下载免费PDF全文 2 Following preloading of strips of guinea-pig gall bladder with 3.6 × 10-7 M (-)-[3H]-noradrenaline for 1 h, the spontaneous overflow of 3H was observed. Cocaine (10-4 M), nortriptyline (10-6 M), (-)-isoprenaline (10-5 M), acetylcholine (10-5 M) and adenosine 5′-triphosphate (ATP, 10-4 M) had no effect on the spontaneous overflow of 3H. KCl (10-1 M), (-)-noradrenaline (10-5 M), (-)-adrenaline (10-5 M), and tyramine (10-5 M) increased the overflow of 3H. These results illustrate similar characteristics of the guinea-pig gall bladder to other noradrenergically-innervated tissues in accumulating and releasing 3H following incubation in the presence of [3H]-noradrenaline.
3 Following incubation in the presence of 3.6 × 10-7 M (-)-[3H]-noradrenaline, field stimulation, at 5 Hz, of strips of gall bladder, in the absence or presence of 10-6 M atropine, increased the overflow of 3H and, simultaneously, induced contractions. The contractile responses to 5 Hz were smaller in the presence than in the absence of 10-4 M lignocaine. Lignocaine (10-4 M) reduced the overflow of 3H evoked by field stimulation at 5 Hz. It is suggested that the contractile responses to 5 Hz are due to nerve stimulation and that the increased overflow of 3H is due to the stimulation of noradrenergic nerves.
4 The overflow of 3H evoked by field stimulation at 5 Hz was unaltered and increased by propranolol (10-6 M) and phentolamine (10-6 M), respectively. Clonidine (5 × 10-5 M) had no effect in the absence but reduced the amount of 3H which overflowed in response to field stimulation at 5 Hz in the presence of 10-6 M atropine. The contractile responses to field stimulation at 5 Hz were reduced by phentolamine (10-6 M) or clonidine (5 × 10-6, 10-5 and 5 × 10-5 M) whether or not atropine (10-6 M) was present. These results illustrate the presence of postsynaptic α-adrenoceptors and suggest the presence of presynaptic α-adrenoceptors in the gall bladder of the guinea-pig.
相似文献 下载免费PDF全文 2 The prolongation of APD and the positive inotropic effect of AP-A (1 × 10-8 M) were augmented by lowering the driving frequency from 2.0 to 0.2 Hz, resulting in an apparent negative staircase of contractile force in this frequency range. When the preparation was driven at an extremely low frequency (0.017 Hz), AP-A did not increase the contractile force, but caused a considerable prolongation of APD.
3 Verapamil (1 × 10-6 M) and nifedipine (1 × 10-6 M) had no apparent influence on the APD prolongation by AP-A (5 × 10-9 M, 1 × 10-8 M). The positive inotropic effect of AP-A was also relatively well maintained even in the presence of these calcium antagonistic drugs when the preparation was driven at a lower frequency (0.2 Hz).
4 Tetrodotoxin (TTX 2 × 10-6 M) and lidocaine (1 × 10-4 M) markedly inhibited both the APD prolongation and the positive inotropic effect of AP-A (1 × 10-8 M).
5 In the presence of ryanodine (2 × 10-6 M), an agent which is known to interfere with calcium release from the intracellular activator pool, AP-A (1 × 10-8 M) failed to cause its positive inotropic effect in spite of the marked prolongation of APD.
6 These results suggest that the effects of AP-A on cardiac muscle are primarily mediated by the fast sodium inward current. Thus, delayed inactivation of sodium inward current may cause APD prolongation, and probably induces an alteration of intracellular calcium kinetics reflected by an increase of contractile force.
相似文献 下载免费PDF全文 2 NG, up to a concentration of 10-5 M, modified neither the membrane potential nor the membrane resistance. Increased concentrations of NG (> 2.8 × 10-5 M) hyperpolarized the membrane, reduced the membrane resistance and enhanced the rectifying property of the membrane measured by depolarization pulses. These phenomena observed with a high concentration of NG are the result of an increase in the K-conductance of the membrane.
3 NG (2.8 × 10-5 M) did not modify the membrane potential displaced by various concentrations of excess [K]o. In low [K]o, NG (2.8 × 10-5 M) hyperpolarized the membrane to a greater extent than that observed in Krebs solution. The effects of NG (10-6 to 2.8 × 10-5 M) on the membrane potential were not modified by simultaneous application of 2 × 10-6 M acetylcholine (ACh).
4 NG (2.8 × 10-6 M) consistently raised the mechanical threshold required for tension development and suppressed the amplitude of the contraction evoked by excess [K]o, ACh or electrical depolarization of the membrane. The dose-response curve shifted to the right in the presence of NG noncompetitively in all the conditions employed to develop the tension.
5 When the tissue was immersed in Ca-free (EGTA) solution, ACh (5 × 10-6 M) evoked a contraction even after the tissue had lost the ability to contract to repetitive applications of 118 mM [K]o in Ca-free (EGTA) solution. However, the tissue finally failed to contract to repetitively applied ACh. At this stage, 2.5 mM [Ca]o evoked a small contraction, after which the response was briefly restored to 5 × 10-6 M ACh. This transient response to ACh was reduced by NG (5.6 × 10-6 M) when NG was added either simultaneously with ACh or with the previous Ca application. However, the inhibition was greater in the former than the latter case.
6 Cysteine (1 to 2 mM), without modifying the membrane potential or membrane resistance, partly restored the contraction evoked by excess [K]o or ACh which had been reduced by NG.
7 The mechanism of action of NG on the smooth muscle cell of the coronary artery of the pig is postulated to be due to a nonselective suppression of the Ca-mobilization from the store site with no noticeable change in the membrane properties.
相似文献 下载免费PDF全文 2 In rat stomach strips, NT elicited a dose-dependent contractile effect in concentrations varying between 1.3 × 10-9 and 5.4 × 10-7 M.
3 The contractile effect of NT (1.3 and 5.4 × 10-8 M) in this tissue was not modified by atropine (3.4 × 10-7 M), methysergide (2.0 × 10-6 M), a mixture of cimetidine (8.0 × 10-6 M) and diphenhydramine (7.8 × 10-6 M), indomethacin (1.4 × 10-5 M), 8-Leu-angiotensin II (1.0 × 10-6 M), glucagon (2.0 × 10-6 M) or somatostatin (3.0 × 10-7 M).
4 Rat stomach strips desensitized by bradykinin (6.1 × 10-6 M) or substance P (7.4 × 10-6 M) maintained their sensitivities to NT (1.3 and 5.4 × 10-8 M).
5 In guinea-pig atria, NT produced a dose-dependent positive inotropic action in concentrations varying between 5.4 × 10-10 and 2.7 × 10-7 M.
6 The inotropic effect of NT (2.7 × 10-9 M) was not influenced by methysergide (2.8 × 10-6 M), atropine (3.4 × 10-7 M), practolol (1.5 × 10-5 M), 8-Leu-angiotensin II (1.0 × 10-6 M), or indomethacin (1.4 × 10-5 M), but it was reduced by 37% by cimetidine (4.0 × 10-5 and 2.0 × 10-4 M). A combination of cimetidine (4.0 × 10-5 M) and diphenhydramine (3.9 × 10-6 M) did not produce a greater inhibition of NT than cimetidine alone.
7 Atria desensitized by bradykinin (6.1 × 10-6 M) or glucagon (2.0 × 10-6 M) maintained their sensitivities to NT (2.7 × 10-9 M). Substance P was inactive both as an agonist or antagonist of NT.
8 These results suggest the existence of specific NT receptors in rat stomach strips and guinea-pig atria.
9 The data derived from our structure-activity study suggest that the minimum structure required for the full stimulation of NT receptors in these two preparations is H-Arg9-Pro10-Tyr11-Ile12-Leu13-OH. The sequence PyroGlu1-Leu2-Tyr3-Glu4-Asn5-Lys6-Pro7-Arg8- and the amino acids Ile12 and Leu13 appear to contribute mainly to the affinity or binding of NT to its receptor. The chemical groups responsible for the full activation (intrinsic activity) of NT receptors seem to be located in the sequence -Arg9-Pro10-Tyr11.
相似文献 下载免费PDF全文 2 Atropine (1 × 10-9 -1 × 10-6M) alone, in the presence of hexamethonium (1 × 10-4M), or phentolamine (1 × 10-6M), inhibited responses to acetylcholine but not to (-)-noradrenaline. The inhibitory effect with the higher concentrations of atropine (1 × 10-8 - × 10-6M), was seen as an increase in the slopes of the concentration-response curves. Atropine (1 × 10-8M) alone inhibited the responses to methacholine and carbachol without altering the slopes of the concentration-response curves.
3 Homatropine (1 × 10-6M) alone had no effect on responses to (-)-noradrenaline and inhibited responses to acetylcholine and methacholine. The inhibitory effect on responses to acetylcholine but not to methacholine, included an increase in the slopes of the concentration-response curves.
4 Neostigmine (1 × 10-6M) alone had no effect on responses to (-)-noradrenaline and potentiated responses to acetylcholine and methacholine. The potentiating effect included an increase in the slopes of the concentration-response curves.
5 In the presence of neostigmine (1 × 10-6M), atropine (1 × 10-9M - 1 × 10-6M) caused a parallel concentration-dependent shift of the concentration-response curves to acetylcholine. The pA2 values, in the presence of neostigmine, were independent of the concentration of atropine and of the agonist (acetylcholine, methacholine, or carbachol) used. In the presence of neostigmine (1 × 10-6M), homatropine (1 × 10-6M) also failed to alter the slopes of the concentration-response curves to acetylcholine and was approximately 100 times less potent than atropine as an antimuscarinic agent.
6 These results illustrate that, in the rat anococcygeus muscle, it is necessary to inhibit acetylcholinesterase before determining the relative potencies of antagonists at muscarinic receptors.
相似文献 下载免费PDF全文 2 At a concentration of 1 × 10-7 M, the amplitude of the first e.j.p. and the enlarged amplitudes of the subsequent e.j.ps evoked by trains of stimuli were reduced consistently by PGI2 or cTxA2. Facilitation was unaffected by either agent.
3 The inhibitory actions of PGI2 were partly overcome by increased concentrations of 5 mM [Ca]o and were accelerated by a reduced concentration of 1.25 mM [Ca]o.
4 The amplitude of the contraction evoked by perivascular nerve stimulation was inhibited to a greater extent by PGI2 than by cTxA2 at concentrations below 1 × 10-6 M.
5 The contraction evoked by 5 × 10-6 M noradrenaline (NA) or excess concentrations of 20.2 mM [K]o was enhanced by 1 × 10-8 M — 1 × 10-6 M cTxA2 and suppressed by 1 × 10-8 M — 1 × 10-6 M PGI2. The minimum concentration of cTxA2 required to produce the contraction was 1 × 10-8 M.
6 These results indicate that transmission at the neuromuscular junction was inhibited consistently by PGI2 or cTxA2, presumably due to inhibition of NA release by suppression of the Ca influx at the nerve terminals. Whereas PGI2 inhibited, cTxA2 enhanced the mechanical response by a direct action on the smooth muscle cells.
相似文献 下载免费PDF全文 2 Each procedure reduced carbachol-induced tone; sympathetic and NANC nerve stimulation were equipotent but both were less effective than sympathomimetic drugs, of which Iso was the better. Both Iso and NA, but not sympathetic nerve stimulation, inhibited the contractions produced by pelvic nerve stimulation in a concentration-dependent manner. Against ACh-induced contractions, only Iso was effective. The effects of NANC nerve stimulation on the motor responses to pelvic nerve stimulation or to ACh were not investigated.
3 The inhibitory effects of sympathetic nerve stimulation, of Iso and of NA were reduced by propranolol (3 × 10-6 M) but unaffected by phentolamine (3 × 10-5 M).
4 In the presence of high (45 mM) concentrations of KCl, Iso and NA produced a concentration-dependent inhibition of tone that was antagonized by propranolol (3 × 10-6 M).
5 Methoxamine (4 × 10-7 to 4 × 10-5 M) and phenylephrine (5 × 10-7 to 5 × 10-5 M) which interact mainly with α1-adrenoceptors, produced only small, transient reductions in carbachol-induced tone which were subject to tachyphylaxis, unlike those produced by Iso and NA. These inhibitory effects were antagonized by phentolamine (3 × 10-6 M) or azapetine (3 × 10-6 M).
6 Phenylephrine (5 × 10-4 M) and high doses (3 × 10-5 M or greater) of NA enhanced the contractile response to pelvic nerve stimulation and, on occasion, produced muscle contraction. These effects were antagonized by phentolamine (3 × 10-6 M).
7 These results suggest that inhibition of the rectococcygeus, a muscle which has no intramural nerve plexus, can be inhibited by stimulation of extrinsic NANC nerves, the transmitter for which is unknown and by sympathetic nerve stimulation via α- and β-adrenoceptors located postsynaptically on the muscle. Excitatory α-adrenoceptors may also be present.
相似文献 下载免费PDF全文 2 The muscular contraction caused by the narcotic analgesics exhibited stereospecificity, with levorphanol being about 50 times more potent than dextrorphan and (-)-methadone 4 times more potent than (+)-methadone. In addition, the rank order in potency of a homologous series of N-alkyl substituted norketobemidones demonstrated that the activity of these compounds in eliciting contractile responses corresponded to that for analgesic efficacy in the rat and also correlated to the ability of these derivatives to inhibit the muscular twitch evoked by electrical stimulation of the guinea-pig ileum.
3 Naloxone blocked the contractile response of the opiates following competitive kinetics; the naloxone pA2 values for morphine, etorphine, levorphanol and methadone were very close, in spite of the marked differences in potency of these agents.
4 The contractile effect of morphine on the rat colon was abolished by incubation of the tissues with tetrodotoxin 2.0 × 10-7 M or by decreasing the external Ca2+ level 100 fold. Increasing the external Ca2+ concentration caused an apparent non-competitive antagonism of the response to morphine.
5 Pretreatment of the tissues with hexamethonium 8.3 × 10-5 M caused a modest antagonism of the morphine effect while atropine 5.8 × 10-7 M did not significantly modify the morphine contractile effect. In contrast, methysergide 10-5 M caused a 10 fold increase in the morphine EC50.
6 Colons from rats rendered tolerant-dependent on morphine were markedly less sensitive to the contractile effects of morphine than those from placebo-treated controls. Tolerance to morphine was also accompanied by an increased sensitivity to the contractile effects of 5-hydroxytryptamine (5-HT).
7 A marked increase in the spontaneous muscular activity of segments of the terminal colon of rats chronically treated with morphine was found to occur upon removal of the residual morphine in the tissues by repetitive washings. The spontaneous activity was arrested by applications of morphine, suggesting that physical dependence can be demonstrated in vitro in this particular preparation.
8 It is concluded that the opiate-induced contractile response is mediated via stereospecific, naloxone-sensitive, opiate receptors and that the muscular response involves the activation of a 5-HT neurone in the nerve terminals of the colon.
相似文献2 The vasodilator effect of histamine was potentiated by papaverine (6.1 × 10-7 M) and IBMX (4.4 × 10-5 M) but inhibited dose-dependently by verapamil (5.1 and 51.0 × 10-7 M).
3 Adenosine-induced vascular relaxations were greatly increased in the presence of papaverine (6.1 × 10-7 M) but significantly reduced in the presence of IBMX (4.4 × 10-5 M) or verapamil (5.1 and 51.0 × 10-7 M).
4 The vasodilatation produced by isoprenaline was increased in the presence of IBMX (4.4 × 10-5 M) or papaverine (6.1 × 10-7 M), but inhibited by verapamil (5.1 and 51.0 × 10-7 M).
5 The vascular relaxant effects of nitroglycerine and papaverine were inhibited in the presence of IBMX (4.4 × 10-5 M) or verapamil (5.1 and 51.0 × 10-7 M). Papaverine (6.1 × 10-7 M) also antagonized nitroglycerine-induced vascular relaxation.
6 The vasodilator effect of IBMX was greatly reduced in the presence of papaverine (6.1 × 10-7 M) or verapamil (5.1 and 51.0 × 10-7 M).
7 The vascular relaxant effect of verapamil was reduced proportionally by raising the extracellular Ca2+ concentration from 1.25 to 5.0 mM while those elicited by histamine, adenosine, isoprenaline, nitroglycerine, papaverine and IBMX were not modified by this procedure.
8 These results were taken as an indication that several vasodilators (e.g. histamine, adenosine, isoprenaline, nitroglycerine, papaverine and IBMX), but not a Ca2+ antagonist such as verapamil, produce a fraction of their vasodilator effects by promoting Ca2+ extrusion from and/or Ca2+ sequestration into the vascular smooth muscle cells, via a cyclic adenosine 3′,5′-monophosphate-dependent mechanism.
相似文献 下载免费PDF全文 2 Renal artery strips from cattle, pre-incubated with [3H]-noradrenaline, were stimulated with 300 pulses at 5 different frequencies, spanning the physiological range, and the efflux of tritium assessed both in the absence and presence of functional presynaptic receptors.
3 Considerable variation in the synaptic level of free and active noradrenaline with increasing frequency was apparent from the rates of development and the magnitudes of the mechanical responses but the overflow of tritium was constant at 1, 2, 10 and 15 Hz and slightly elevated at 5 Hz, providing no evidence for presynaptic modulation of release.
4 Phenoxybenzamine (3.3 × 10-5 M) enhanced the overflow of tritium most at the lowest frequency tested and to a similar extent at the other test frequencies, except 10 Hz where its effect was slightly reduced.
5 The conditions of the present experiments appeared optimal for the operation of the negative feedback system and the failure to observe an increased effectiveness of the antagonist with increasing frequency indicates that the physiological relevance of such a system is highly questionable and suggests that it may not function at all.
相似文献 下载免费PDF全文 2 5-HT contracted the dog isolated femoral artery and saphenous vein over the concentration-range 1.0 × 10-8 to 5.0 × 10-6 mol/l.
3 In the femoral artery methysergide and cyproheptadine were potent, competitive and specific antagonists of the contractile responses to 5-HT, with pA2 values of 8.52 and 8.55 respectively.
4 In the saphenous vein, methysergide was only a weak antagonist of 5-HT. In addition, it was an agonist over the concentration-range 5.0 × 10-8 to 1.0 × 10-5 mol/l. Cyproheptadine was a weak and unsurmountable antagonist of contractile responses to 5-HT and methysergide.
5 Contractile responses to 5-HT and methysergide in the saphenous vein were not antagonized by morphine (3.0 × 10-5 mol/l), indomethacin (5.0 × 10-5 mol/l), phentolamine (5.0 × 10-7 mol/l), propranolol (1.0 × 10-6 mol/l), atropine (1.0 × 10-6 mol/l), mepyramine (1.0 × 10-6 mol/l) or cimetidine (1.0 × 10-5 mol/l).
6 In the external carotid and lingual arteries the pattern of activity obtained with methysergide and cyproheptadine was the same as that in the femoral artery, while in the auricular artery the pattern of activity was the same as that in the saphenous vein.
7 The results are consistent with the hypothesis that there are two types of receptor mediating 5-HT-induced vasoconstriction in dog vasculature. One type, characterized by the pattern of activity obtained in the femoral artery, is like the previously described `D-receptor'. The other type, characterized by the pattern of activity obtained in the saphenous vein, has not been described before. The verification of this hypothesis requires the identification of a specific antagonist of 5-HT and methysergide in the saphenous vein.
相似文献 下载免费PDF全文 2 Cph ≥ 10-6M reduced the amplitude of normal spontaneous contractions and concurrently decreased the number of action potentials occurring with each slow-wave of depolarization (sucrose-gap recordings). These inhibitory effects of Cph were antagonized by increasing the medium [Ca] three fold to 7.68 mM.
3 Intracellular recordings showed that Cph ≥ 2 × 10-6M decreased the amplitude and extended the duration of the action potential. These effects were only partially reversible in normal medium whereas large overshooting action potentials were again seen in 7.68 mM Ca medium.
4 High frequency mechanical activity was produced by inclusion of veratridine 5 × 10-6M in the perfusate. Low concentrations of Cph (≥ 10-7M) reduced the amplitude of such contractions at a faster rate than they did normal spontaneous contractions.
5 At concentrations between 10-7 and 10-6M, Cph fully reduced the tonic component of contractions elicited in 112 mM isotonic KCl whilst having little or no effect on either (i) the initial phasic KCl contraction or (ii) the `repolarization contracture' normally produced on wash-out of the KCl or (iii) the spontaneous contractions before and after KCl treatment. In contrast, at Cph 2 × 10-6M, the repolarization contracture, as well as the isotonic KCl contraction, was totally blocked whereas spontaneous contractions were still unaffected. Progressively higher Cph concentrations inhibited all components of this contractile cycle.
6 Dose-response curves for the rate of drug-induced relaxation of tonic contractures produced in hypertonic 42.7 mM high-potassium medium, showed the calcium antagonistic potency of Cph to be intermediate between that of chlorpromazine and D600. The minimum Cph concentration for effect lay between 1 and 5 × 10-7M, and the effects of Cph 2 × 10-6M (approximately the ID50) were totally antagonized by 12.8 mM Ca.
7 By means of a lanthanum wash procedure, Cph ≥ 2 × 10-6M was found to decrease the 45Ca uptake occurring into strips of taenia coli in normal medium, although the maximum effect (at Cph 10-5M) amounted to only 25% inhibition of the uptake occurring into control strips (also found with D600). The increased uptake occurring in hypertonic 44.7 mM high-potassium medium was inhibited in a dose-dependent manner by Cph 1 × 10-7M.
8 The results are consistent with an action of Cph in reducing the flow of Ca2+ through voltage-dependent Ca channels in the smooth muscle cell membrane. It is suggested that the interaction of Cph molecules with such sites is dependent upon membrane potential as well as drug concentration.
相似文献2 Ketamine was found to inhibit development of spontaneous mechanical activity and lower basal tension. This action took place with ketamine concentrations found in anaesthetic plasma concentrations, i.e., 1 × 10-5 to 2 × 10-4 M.
3 Ketamine (10-5 to 10-3 M) dose-dependently attenuated contractions induced by adrenaline, noradrenaline, angiotensin II, vasopressin and KCl. These inhibitory actions were observed with ketamine added either before or after the induced contractions.
4 Ca2+-induced contractions of K+-depolarized aortae and portal veins were also attenuated, dose-dependently, by ketamine.
5 In contrast to the above inhibitory actions, ketamine (2 × 10-6 to 1 × 10-4 M) was found to potentiate specifically 5-hydroxytryptamine(5-HT)-induced contractions of both aortic and venous smooth muscle. However, this was only observed if ketamine was added after 5-HT had initiated a contractile response.
6 All of the inhibitory, as well as 5-HT-potentiating, effects were completely, and almost immediately, reversed upon washing out the anaesthetic from the organ baths.
7 A variety of pharmacological antagonists failed to mimic or affect the inhibitory effects induced by ketamine.
8 These data suggest that rat plasma concentrations of ketamine commonly associated with induction of surgical anaesthesia can induce, directly, relaxation and contractile potentiation of vascular muscle.
9 These diverse findings may aid in explaining the well-known biphasic pressor actions of ketamine.
相似文献 下载免费PDF全文 2 At low concentrations (between 5 × 10-10 and 10-9 M) At II induces an acceleration of spontaneous action potential (AP) discharge without change in the resting membrane potential. The frequency and size of the associated contractions are simultaneously augmented. Under these conditions the size of the spikes is not affected, thus suggesting that At II triggers the release of Ca2+ from internal stores.
3 The increase in AP discharge rate produced by low concentrations of At II results from an acceleration of the pacemaker potential. Furthermore, in the presence of 10 mM tetraethylammonium (TEA), there is an acceleration of the repolarizing phase of AP.
4 Ouabain (10-3 M) inhibits the increase in rhythmic activity induced by low concentrations of At II (in the presence of 10 mM TEA), thus suggesting that the Na-K pump is directly or indirectly involved in this action of the peptide.
5 At higher concentrations, At II produces a concentration-dependent depolarization with an EC50 of 1.2 × 10-8 M and a maximum of 10-7 M. The associated contraction has an EC50 of 3.3 × 10-8 M and a maximum of 3 × 10-7 M.
6 Ouabain (3 × 10-3 M) depolarizes the cell membrane. Under these conditions, At II (10-7 M) has a slight depolarizing effect, but it still produces a large tonic contraction.
7 It is concluded, that At II acts on different steps of excitation-contraction coupling, depending on the concentration. At low levels, the peptide mainly accelerates spike discharge, through a mechanism involving the Na-K pump. At higher concentrations, At II depolarizes the cell membrane. The contraction is then activated by the influx of Ca2+ due to secondary AP discharge and the release of Ca2+ from intracellular stores. Pharmacomechanical coupling has an important role in the triggering of contractions both at high and at low concentrations of At II.
相似文献 下载免费PDF全文 2 SP (10-13-10-10M) induced a phasic contraction of longitudinal muscle strips, but did not change the muscle tone of circular muscle strips, in concentrations up to 10-8M.
3 SP (10-10-10-8M) evoked three different membrane responses in longitudinal muscle cells: (i) bursts of spike discharges with no significant change in the membrane potential and input membrane resistance; (ii) bursts of spike discharges with a small but clear depolarization of the membrane and increase in the input membrane resistance; (iii) slow waves with no change in the membrane potential.
4 In the circular muscle cells, low concentrations of SP (<10-8M) did not affect the membrane potential or the spikes, but SP (10-7M) increased the spike discharges with no significant change in the membrane potential.
5 SP (10-10M) reduced the threshold depolarization required for the generation of action potentials with no change in membrane potential of the longitudinal muscle cells.
6 Pretreatment with atropine (5 × 10-6M), tetrodotoxin (TTX 10-6M) or baclofen (4.7 × 10-6M) had no effect on the excitatory actions of SP on the smooth muscle cells of longitudinal and circular muscle strips.
7 Excitatory actions of SP on the membrane potential or spike activities of longitudinal muscle cells were preserved in NaCl but not in Ca-deficient solution.
8 SP (10-10-10-9M) enhanced the amplitude of the excitatory junction potentials (e.j.ps) evoked by electrical field stimulation in longitudinal muscle cells with no change in the membrane potential and input resistance. SP (10-10-10-9M), however, did not change the amplitude of inhibitory junction potentials (i.j.ps) recorded from the circular muscle cells.
9 These results indicate that SP in relatively low concentrations acts on both smooth muscle cells and on excitatory neuro-effector transmission in the longitudinal muscle; the main site of the action of SP is probably the muscle membrane.
相似文献 下载免费PDF全文 2 Rat occipitocortical slices were preincubated with [3H]-amezinium 0.03 μM and then superfused and stimulated electrically (3 Hz for 3 min). The stimulation-evoked overflow of tritium was measured in six groups of slices: from saline-pretreated rats; from saline-pretreated rats, the slices being exposed to exogenous noradrenaline before preincubation with [3H]-amezinium; from saline-treated rats, slices from which were exposed simultaneously to noradrenaline and cocaine before preincubation with [3H]-amezinium; from rats in which noradrenaline stores had been depleted by pretreatment with α-methyltyrosine (α-MT); from α-MT-treated rats, the slices being exposed to noradrenaline before preincubation with [3H]-amezinium; and from α-MT-treated rats, slices from which were exposed to noradrenaline plus cocaine before preincubation with [3H]-amezinium.
3 The stimulation-evoked overflow of tritium, expressed as a percentage of the tritium content of the tissue, was 1.15% in slices from saline-pretreated rats, and was similar in slices from saline-pretreated rats after exposure to noradrenaline or noradrenaline plus cocaine. It was 2.56% in slices from α-MT-treated rats, 1.20% from α-MT-treated rats after exposure to noradrenaline, and 2.88% from α-MT-treated rats after exposure to noradrenaline plus cocaine.
4 Yohimbine 0.1 and 1 μM increased the stimulation-evoked overflow of tritium in slices from all groups of saline-pretreated rats and in those slices from α-MT rats that had been in contact with exogenous noradrenaline. Yohimbine did not change the evoked overflow in slices from α-MT rats that had not been exposed to noradrenaline, or had been exposed to noradrenaline plus cocaine.
5 Clonidine 0.01-1 μM decreased the stimulation-evoked overflow of tritium moderately in slices from saline-pretreated rats, markedly in slices from α-MT-treated rats, and moderately again when the latter slices had been exposed to noradrenaline.
6 It is concluded that the action potential-evoked release of [3H]-amezinium as well as the modulation of this release by yohimbine and clonidine depend on the presence or absence of α-adrenergic autoinhibition caused by the co-secretion of noradrenaline. When there is co-secretion of noradrenaline, the evoked release of [3H]-amezinium is relatively small, yohimbine increases the release, and clonidine can cause only moderate inhibition. When there is no or very little co-secretion of noradrenaline, the evoked release of [3H]-amezinium is at least doubled, yohimbine causes no further increase and clonidine produces strong inhibition.
相似文献 下载免费PDF全文 2 The amplitudes of nerve-mediated and drug-induced responses were considerably potentiated by substance P (SP) in the dose range 10-12 to 10-7 M. Higher concentrations of SP were directly spasmogenic. The sensitizing property of SP was dose-dependent and was usually well maintained, but always disappeared quickly on washing the preparation. In some experiments SP facilitated the twitch, but not the subsequent phase of the electrically-induced contraction or the response to externally applied noradrenaline.
3 Phentolamine (10-6 M) failed to block this effect of SP, but itself potentiated the nerve-mediated twitch, and completely abolished the sustained secondary contraction.
4 Desmethylimipramine (10-6 M) enhanced the delayed contraction but not the immediate contraction.
5 The uptake of tritiated noradrenaline (3 × 10-7 M) by vasa was inhibited by desmethylimipramine (10-6 M) and increased by nialamide (3 × 10-5 M), but was not modified by SP (10-6 M).
6 Nerve-mediated release of accumulated radioactivity was accelerated by phentolamine, but not by SP or desmethylimipramine.
7 These findings suggest that SP sensitizes the muscle cells to depolarizing stimuli but that it has no facilitatory effect on sympathetic neural elements.
相似文献 下载免费PDF全文 2 The membrane potential and length constant of smooth muscle cells of the guinea-pig pulmonary artery were -53.2 mV and 1.2 mm, respectively, and those of the portal vein were -52.6 mV and 0.71 mm, respectively. The membrane was electrically quiescent in the pulmonary artery and it was electrically active in the portal vein.
3 Both 4-AP and procaine depolarized the membrane, increased the membrane resistance and suppressed the rectifying properties in both tissues. Both agents evoked a graded response from the muscle membranes of the pulmonary artery by outward current pulse. Procaine had a greater effect than 4-AP on the above membrane properties.
4 4-AP (10-5 M) produced contraction without depolarization of the membrane. The contraction evoked by 10-5 M 4-AP was completely suppressed but that evoked by 5 × 10-4 M 4-AP was only partly suppressed by phentolamine (10-7 M). However, the contraction evoked by procaine was not suppressed by phentolamine.
5 4-AP enhanced but procaine suppressed the amplitude of 118 mM [K]0-induced contraction.
6 The results suggest that 4-AP and procaine suppress K-conductance of the muscle membrane, and 4-AP but not procaine increases noradrenaline release from the nerve terminal. Presumably intracellular free Ca concentrations are also modified by these agents. The effects of 4-AP and procaine on the vascular muscle were compared with those on other excitable tissues.
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