Further studies on the effects of disodium cromoglycate on guinea pig ileum

Transmural electrical stimulation was carried out on innervated strips of the longitudinal muscle of guinea pig ileum. Disodium cromoglycate (DSCG) inhibited the electrically induced contractions.Five minutes later, prostaglandin E₂ (2.5 ng/ml) was added to the bath and it reversed the action of DSCG. Furthermore, DSCG inhibits significantly the guinea pig ileum contractions induced by nicotine and also those induced by histamine and acetylcholine on ileum denervated by cooling.These results suggest that DSCG effects on guinea pig ileum contraction are mediated by membrane-stabilizing properties of this drug on smooth muscle fibres as well as on myenteric plexus.     

Differentiation between pre- and postjunctional α-receptors in guinea pig ileum and rabbit aorta

Electric stimulation of proximal and terminal guinea pig ileum induced contractions which were mediated by stimulation of cholinergic neurons. After blocking β-receptors, prejunctional α-receptors mediating inhibition could be studied in these neurons. In proximal ileum the order of potencies of the following agonists was: clonidine (8)* < epinephrine (3) < oxymetazoline (2)< norepinephrine (1)< phenylephrine (0.02). The intrinsic activities of clonidine and phenylephrine were not maximal. In electrically stimulated terminal ileum practically identical results were obtained on the prejunctional α-receptor except that phenylephrine was ineffective; the drug instead acted as a competitive blocker against norepinephrine. After blocking cholinergic receptors with atropine, excitatory α-receptors located postjunctionally in the smooth muscle cells of terminal ileum could be studied. Under these conditions the order of potencies of the agonists was: oxymetazoline (40)< epinephrine (7) < phenylephrine (4)<norepinephrine (1)< clonidine (0.2). In contracting postjunctional α-receptors in rabbit aorta the order of potencies was: oxymetazoline (5) < norepinephrine (1) < epinephrine (0.7) < phenylephrine (0.2) > clonidine (0.04). On the postjunctional α-receptor in terminal guinea pig ileum phentolamine was 55 fold more effective in blocking the response of norepinephrine than it was on blocking the response on the prejunctional receptor of the same preparation. Phenoxybenzamine (4 times 10^-8 M) was ineffective on the prejunctional α-receptor of the cholinergic neuron, while it blocked the postjunctional α-receptor of smooth muscle in guinea pig terminal ileum noncompetitively. It is suggested that the differences in the activities of clonidine and phenylephrine between prejunctional α-receptors located to cholinergic neurons and postjunctional α-receptors located to smooth muscle cells was due to a pharmacological difference between the receptors. The results obtained with the blockers support this suggestion.     

Pharmacological characterization of ketotifen effects on guinea pig ileum

The effects of Ketotifen (Ke) on the contraction of isolated guinea pig ileum induced by electrical stimulation, nicotine or acetylcholine have been investigated. Ke (10(-6)-10(-5) M) inhibited electrically-induced contractions. Prostaglandin F2 alpha, when added to the bath shortly after Ke, reversed this effect. Furthermore, Ke significantly inhibits guinea pig ileum contractions induced by nicotine and acetylcholine both on innervated and denervated ileal strips. These results suggest that Ke influence on ileum contractions is mediated either by inhibition of acetylcholine release from postganglionic parasympathetic fibres of ileum or by anticholinergic effect (atropine-like action). The inhibitory effect of Ke against acetylcholine-induced contractions is in favor of the latter possibility, although nonspecific membrane stabilizing effect might be also involved in the mode of Ke action.     

Sensitizing ability of derivatives of picryl chloride after exposure of mice on the skin and in the lung

BL-5255 inhibited release of preformed mediators from passively sensitized mast cells in the rat peritoneal cavity, chopped monkey lung or human lung tissue. The compound failed to block rat cutaneous reactions elicited by histamine or serotonin. It exhibited weak to no ability, depending on the mediator employed, to block contraction of isolated guinea pig ileum or tracheal tissue. At concentrations of 1 microM or greater, BL-5255 itself was contractile to the ileum but not to the quiescent or submaximally contracted trachea. The compound relaxed spontaneously contracting rabbit jejunum muscle but at doses not likely to be achieved in vivo. Phosphodiesterase activities in extracts of rat and human lung were inhibited at concentrations greater than those required to inhibit mediator release.     

Different effects of neuropeptide Y on electrically induced contractions in the longitudinal and circular smooth muscle layers of the female rabbit urethra

The effects of neuropeptide Y (NPY) on preparations of isolated longitudinal and circular smooth muscle from rabbit urethra were studied. In both types of muscle, electrically induced contractions and relaxations could be abolished by tetrodotoxin, (TTX). In the longitudinal muscle preparations the contraction was slightly reduced by prazosin, but markedly reduced by scopolamine and NPY. The NPY effect was not influenced by pretreatment with rauwolscine. Pretreatment with NPY had no effect on contractions induced by noradrenaline (NA) or carbachol and the peptide did not relax preparations contracted by these agents. In circular muscle an initial, fast response, not sensitive to prazosin or scopolamine was occasionally observed following electrical stimulation. A slow contraction component was regularly seen; this response was abolished by prazosin. Neuropeptide Y did not influence any of these responses. The preparations were concentration-dependently contracted by NA, whereas carbachol had no effect. Pretreatment with NPY did not affect contractions induced by NA, nor did the peptide relax NA-contracted preparations. In neither longitudinal nor circular muscle strips did NPY affect the electrically induced TTX sensitive relaxation of NA-contracted preparations. The results suggest that in the rabbit urethra NPY reduces contractions in the longitudinal muscle layer by selectively inhibiting the release of acetylcholine from cholinergic nerves. Neuropeptide Y did not appear to have any significant postjunctional effects nor to interfere with the release, or effects of NA or other transmitter agents. The physiological importance of the urethral effects of NPY remains to be established.     

Isolation and contractile properties of single smooth muscle cells from guinea pig taenia caeci

A method for the isolation of single smooth muscle cells from guinea pig taenia caeci is described. The single cells were prepared by digestion with 0.3% collagenase and 0.6% trypsin inhibitor in Ca2+-free solution. This procedure produced a high yield of intact cells. Most cells obtained by this procedure were relaxed and showed large contractile responses to excitatory stimulus. Maximal responses of the single cells to acetylcholine (ACh), histamine, and high K+ were attained within 20 sec, and the per cent decrease in cell length was 30-40%. Times for maximal responses of the single cells were shorter than those of the muscle strips. Single cells exhibited a dose-dependent graded response to calcium under depolarized conditions, ACh, histamine, and high K+, and a voltage- and duration-dependent response to electrical stimulation. The ED50s of ACh in the single cells and in the muscle strips were about 2 X 10(-8) and 1.5 X 10(-7) M, respectively. The muscle strips had a lower sensitivity than the single cells to ACh. The generally smooth surface of the relaxed cell contrasted with the numerous evaginations present on the fully contracted cell. I believe that single smooth muscle cells isolated from guinea pig using my technique are, at present, better for physiological and pharmacological studies than are cells isolated using other techniques.     

The origin of acetylcholine released from guinea-pig intestine and longitudinal muscle strips

1. Strips of longitudinal muscle can be obtained from guinea-pig ileum either retaining or free from Auerbach's plexus.

2. The denervated strip is unresponsive to electrical stimulation by brief shocks, whether given singly or in trains; it also fails to respond to nicotine or dimethylphenylpiperazinium iodide (DMPP), and eserine causes no spasm.

3. Denervated strips neither contain detectable acetylcholine (< 0·4 ng/mg), nor release it spontaneously (< 5 pg/mg/min) or in response to stimulation (< 31 pg/mg/min). The acetylcholine metabolism of the innervated strip is therefore that of the adherent Auerbach's plexus. Innervated strips had a mean acetylcholine content of 28 ng/mg, a mean resting output of 94 pg/mg/min and an output in response to stimulation at 10 c/s of 700-1200 pg/mg/min.

4. By comparing the responses of innervated and denervated strips it was concluded that arecoline, methylfurmethide, α,β-ethylal-γ-tri-methylammonium propanediol iodide (2268 F), muscarine, histamine, tremorine, oxytocin, and substance P, like acetylcholine, act primarily on the smooth muscle directly; and that angiotensin, barium, potassium, m-bromophenyl choline ether and 5-hydroxytryptamine have a progressively increasing proportionate effect on the nerve plexus. Nicotine and DMPP were inactive in the absence of the plexus.

5. The longitudinal muscle with its accompanying plexus contains about one quarter of the acetylcholine of the whole ileum, and is responsible for about one fifth of the output to electrical stimulation.

6. The volley output of acetylcholine by the innervated strip declines sharply as rate of stimulation increases. Output of acetylcholine was reduced by morphine and by cocaine, particularly when resting or when stimulated at low rates.

7. Acetylcholine output by whole ileum from guinea-pig declines in the absence of glucose, but is insulin-independent. Output by strips of ileum from rats made diabetic with alloxan was similar to that from normal rats.

8. The similarity in properties of acetylcholine output from innervated strips, where it must come from nervous tissue, to that from whole ileum, and the insulin-independence of output from whole ileum suggest that the whole of the acetylcholine output of intestine is nervous in origin.

9. Comparison of the acetylcholine metabolism of the innervated strip with that of the superior cervical ganglion suggests that the typical features of the former (high resting output, high volley output at low rates, low minute output at high rates of stimulation, and sensitivity to morphine) may be linked with the absence of specialized neuro-effector junctions and represent a relatively primitive transmission process.

     

Neuromuscular actions of endothelin on smooth, cardiac and skeletal muscle from guinea-pig, rat and rabbit

The peptide endothelin (human, porcine) was investigated for effects on basal muscle tone and on responses to transmural nerve stimulation in a series of smooth muscle preparations, as well as in guinea-pig atrium and rat and guinea-pig diaphragm. Endothelin lacked effect on basal tone or on spontaneous and electrically driven contractions in skeletal and atrial muscle. It contracted guinea-pig ileum, pulmonary and femoral arteries, rat anococcygeus, vas deferens and urinary bladder and rabbit taenia coli, whereas guinea-pig taenia was relaxed. Guinea-pig urinary bladder and vas deferens and rabbit iris sphincter were unaffected up to 3 x 10(-8) M. Endothelin thus has a unique pattern of smooth muscle effects, exhibiting mostly contractile but also relaxing effects. Endothelin modified contractile responses to transmural nerve stimulation, yielding marked and persistent enhancement, in guinea-pig and rat vas deferens, and enhancement also in guinea-pig pulmonary artery. In guinea-pig and rat vas deferens the response to exogenous ATP was increased by endothelin, thus suggesting a strong post-junctional enhancement of neurotransmission. In guinea-pig ileum nerve-induced responses were inhibited by endothelin, whereas exogeneous acetylcholine was enhanced, an effect suggesting a simultaneous pre-junctional inhibition and post-junctional enhancement. The Ca2+ channel blocker felodipine counteracted the stimulatory effects of endothelin on tone and transmurally induced contractions. Tachyphylaxis to endothelin action was sometimes evident, but the anococcygeus being less prone to this might be useful for studies on endothelin antagonism. Endothelin thus has prominent post-junctional, and also probably pre-junctional, effects, lending further support for a distinct biological role of this peptide.     

Further evidence that substance P partly mediates the action of cholecystokinin octapeptide (CCK-8) on the guinea pig ileum but not gall bladder: studies with a substance P antagonist

The substance P antagonist, [D-Pro4-D- Trp7 ,9,10]substance P4-11, caused a pig parallel shift to the right of the cholecystokinin (CCK-8) dose-response curve in guinea pig ileum longitudinal muscle without changing the maximal contraction. The shift of the CCK-8 dose response was markedly reduced after desensitization of the tissues to substance P (SP). The SP antagonist had no effect upon CCK-8 responses of the guinea pig gall bladder, [125I]CCK pancreatic binding or contractions of the guinea pig ileum produced by acetylcholine or electrical stimulation. The data provide additional evidence for the involvement of SP in the action of CCK-8 on the guinea pig ileum but not the gall bladder.     

Contractile effects of endothelin-I and localization of endothelin binding sites in rabbit lower urinary tract smooth muscle

In isolated rabbit bladder and urethral smooth muscle, endothelin-1 caused concentration-related, slowly developing contractions that were difficult to wash out. Relative to contractions induced by K⁺ (124 mM), contractions in bladder preparations reached a higher amplitude than in urethral preparations. There was a marked tachyphylaxis to the effects of the peptide. The endothelin-l-induced contractions were not significantly affected by phentolamine or indomethacin in the urethra, or by scopolamine or indomethacin in the bladder. Incubation for 30 min in a Ca²⁺-free solution abolished the endothelin-l-induced contractions. Nifedipine did not affect the actions of endothelin-1 in the urethra but had a marked inhibitory action on its effects in the bladder. In the presence of endothelin-1, Ca²⁺-induced contractions were significantly blocked by nifedipine in the bladder but not in the urethra. Urethral preparations at resting tension responded to electrical stimulation by tetrodotoxin-sensitive, frequency-dependent contractions sensitive to α-adrenoceptor blockade. Pretreatment with endothelin-1 (10^-9′ M) produced a significant increase in the nerve-induced contractions but had no significant effect on contractions induced by exogenous noradrenaline. Endothelin-1 did not affect spontaneous or stimulation-induced efflux of ³H-labelled noradrenaline in urethral smooth muscle. Preparations contracted by endothelin-1 were frequency-dependently relaxed by electrical stimulation. The peptide had no significant effect on the responses induced by electrical stimulation in the bladder preparations. In both bladder and urethra, [¹²⁵]endothelin-l binding sites were found mainly in the outer longitudinal muscle layer, in vessels and in the submucosa. The highest density of binding sites appeared to be in vessels and the outer muscle layer in both types of muscle. The results suggest that in the rabbit both bladder and urethral smooth muscle contain binding sites for endothelin. The peptide has contractant effects dependent on extracellular calcium in both types of tissue, but voltage-operated calcium channels seem to involved in activation only of bladder smooth muscle. The functional importance of endothelin-1 in the rabbit lower urinary tract remains to be elucidated.     

Inhibition of acetylcholine release in guinea pig ileum by adenosine.

The effect of adenosine on cholinergic neuroeffector transmission was studied in the isolated guinea pig ileum. Adenosine caused a dose-dependent and inverse frequency-dependent inhibition of contraction responses to transmural nerve stimulation. Blockade of adrenergic neurotransmission did not alter the inhibitory effect of adenosine. Adenosine also inhibited contraction responses to serotonin, angiotensin and high potassium, but not the responses to acetylcholine, histamine or direct electrical stimulation of the smooth muscle cells. Adenosine had little effect on basal outflow of acetylcholine but inhibited markedly and reversibly the release of acetylcholine induced by nerve stimulation. Acetylcholine was determined with gas chromatography-mass spectrometry. The results provide direct evidence that adenosine inhibits cholinergic neuroeffector transmission in the gut by a prejunctional action on acetylcholine release. This may be of functional importance since adenine compounds are released during stimulation of intestinal nerves.     

A simple and efficient method for studying neurotransmitter release in vitro by a radiotracer technique

A method which allows measurement of neurotransmitter release from isolated preparations has been developed. With this method release of ³H-acetylcholine from guinea pig ileum and rabbit jejunum could be studied after preincubation of the preparations with ³H-choline. The release of noradrenaline from guinea pig vas deferens could also be measured after preincubation with ³H-noradrenaline. The method is based on a device which allows experiments on 4 preparations at the same time, including incubation, field stimulation and collection of fractions for counting of radioactivity. With the purpose of obtaining a simple and inexpensive device for stimulating the tissue preparations electrically, a physiological stimulator distributor (PSD) was constructed. It is concluded that the described method constitutes an inexpensive simple and quick means of studying neurotransmitter release from isolated tissues.     

Investigation into the effects of mosapride on motility of Guinea pig stomach,ileum, and colon

Mosapride citrate (Mosapride) is a new prokinetic agent that enhances the gastrointestinal (GI) motility by stimulation of 5-HT4 receptors. This agent stimulates acetylcholine release from enteric cholinergic neurons in the GI wall. It was reported in several studies that mosapride selectively enhanced the upper, but not lower, GI motor activity. However, in these studies other 5-HT4 receptor agonists exerted stimulating effects on the motility of the colon. Moreover, it is well known that the receptors of 5-HT4 are also located in the colon. The purpose of this study was to estimate the effect of mosapride on the motility of the stomach, ileum and colon in the guinea pig and to investigate whether or not mosapride influenced the colonic motility. Mosapride significantly increased the amplitude of the contraction waves in the guinea pig stomach by electrical stimulation. In addition, it significantly increased the number of peaks, the area under the curve and the propagation velocity of the peristaltic contraction of the guinea pig ileum in a concentration dependent fashion. Mosapride also significantly shortened the transit time of the guinea pig colon. Accordingly, we concluded that mosapride exerted prokinetic effect on the entire GI tract of the guinea pig. Based on the possibility of similar results in humans, we suggest the potential use of mosapride for lower GI motor disorders such as constipation and upper GI motor disorders such as gastroesophageal reflex disease or gastroparesis.     

Contractile effects of endothelin-1 and localization of endothelin binding sites in rabbit lower urinary tract smooth muscle

In isolated rabbit bladder and urethral smooth muscle, endothelin-1 caused concentration-related, slowly developing contractions that were difficult to wash out. Relative to contractions induced by K+ (124 mM), contractions in bladder preparations reached a higher amplitude than in urethral preparations. There was a marked tachyphylaxis to the effects of the peptide. The endothelin-1-induced contractions were not significantly affected by phentolamine or indomethacin in the urethra, or by scopolamine or indomethacin in the bladder. Incubation for 30 min in a Ca2(+)-free solution abolished the endothelin-1-induced contractions. Nifedipine did not affect the actions of endothelin-1 in the urethra but had a marked inhibitory action on its effects in the bladder. In the presence of endothelin-1, Ca2(+)-induced contractions were significantly blocked by nifedipine in the bladder but not in the urethra. Urethral preparations at resting tension responded to electrical stimulation by tetrodotoxin-sensitive, frequency-dependent contractions sensitive to alpha-adrenoceptor blockade. Pretreatment with endothelin-1 (10(-9) M) produced a significant increase in the nerve-induced contractions but had no significant effect on contractions induced by exogenous noradrenaline. Endothelin-1 did not affect spontaneous or stimulation-induced efflux of 3H-labelled noradrenaline in urethral smooth muscle. Preparations contracted by endothelin-1 were frequency-dependently relaxed by electrical stimulation. The peptide had no significant effect on the responses induced by electrical stimulation in the bladder preparations. In both bladder and urethra, [125]endothelin-1 binding sites were found mainly in the outer longitudinal muscle layer, in vessels and in the submucosa. The highest density of binding sites appeared to be in vessels and the outer muscle layer in both types of muscle. The results suggest that in the rabbit both bladder and urethral smooth muscle contain binding sites for endothelin. The peptide has contractant effects dependent on extracellular calcium in both types of tissue, but voltage-operated calcium channels seem to involved in activation only of bladder smooth muscle. The functional importance of endothelin-1 in the rabbit lower urinary tract remains to be elucidated.     

Pre- and postjunctional effects of prostaglandin E2, prostaglandin synthetase inhibitors and atropine on cholinergic neurotransmission in guinea pig ileum and bovine iris

The effects of prostaglandin E2, arachidonic acid, prostaglandin synthetase inhibitors and atropine on cholinergic neuromuscular transmission were examined in isolated guinea pig ileum longitudinal muscle and bovine iris sphincter muscle. Prostaglandin E2 and arachidonic acid markedly enhanced contraction responses induced by nerve stimulation. In addition, prostaglandin E2, enhanced contraction responses to acetylcholine and direct muscle stimulation, approximately to the same extent as those to nerve stimulation. Prostaglandin synthetase inhibitors (indomethacin, meclofenamic acid and eicosatetraynoic acid) very effectively reduced contraction responses to nerve stimulation or acetylcholine, and they annulled the stimulant effect of arachidonic acid. Basal and nerve-induced efflux of acetylcholine from the eserinized tissues, as measured by mass fragmentography, was unaltered by prostaglandin E2, but diminished slowly during indomethacin. Subsequent prostaglandin administration caused a slight increase of nerve-induced release of acetylcholine. Atropine markedly increased overflow of acetylcholine form stimulated preparations of both types. This indicates that muscarinic receptors, causing diminished acetylcholine release in eserinized tissue, may be present also at postganglionic terminals. During atropine, an effect of prostaglandin E2 on acetylcholine release could still not be seen. Thus, using physicochemical determination of acetylcholine, we could not verify earlier reports, employing bioassay, claiming enhanced release of transmitter during prostaglandin E2 treatment. However, it seems likely that prostaglandin E2 takes part in the regulation of contractility and tone of the smooth muscle cells.     

Agonist and antagonist characterization of the P2-purinoceptors in the guinea pig ileum

When adenine nucleotides were administered to isolated guinea pig ileum longitudinal muscle, two immediate effects were observed: a contractile effect and a concomitant inhibition of the responses elicited by transmural nerve stimulation. At concentrations up to 10^-4m the order of potency for the contractile effect was α,β-MeADP =α,β -MeATP > ADP = ATP = AMPPNP =β,t -MeATP > 2′-deoxy AMP = 2′-deoxy ADP. AMP and adenosine did not show any contractile effect, whereas both compounds dose-dependently and reversibly inhibited the nerve-induced contractile responses. ADP, ATP, β,t -MeATP and AMPPNP also inhibited contractile responses to transmural nerve stimulation, whereas 2′-deoxy AMP, 2′-deoxy ADP, α,β -MeADP and α,β -MeATP showed but weak inhibitory effects, 2′-deoxyadenosine, IMP, IDP, ITP, 8-BrATP and TDP lacked significant contractile effects and did not exert a significant inhibition on nerve-induced contractions. p-chloromercuribenzene sulphonic acid (PCMBS) irreversibly antagonized the contractile effects of ADP, ATP and the α,β -methylene derivatives, whereas dantrolene sodium, tetrodotoxin, scopolamine and 8-p-sulphophenyltheophylline were without effect on nucleotide-induced contractions. The contractile effect of ADP or ATP was unaffected by indomethacin, whereas the contractile effect by α,β -methylene derivatives was abolished by indomethacin. ADP, ATP and α,β -MeADP enhanced contractile responses to exogenous acetylcholine, α,β-MeADP being most effective. This enhancement was blocked by indomethacin. We suggest that ADP and ATP contracted the guinea pig ileum by an action at postjunctional P₂-purinoceptors with different characteristics from prejunctional P₁-purinoceptors. The α,β-methylene analogues seemed to act at least at one different excitatory site and promotion of prostaglandin biosynthesis was critical for their effect.     

Effects of neurotransmitter release on mucosal transport in guinea pig ileum

Scorpion venom (Leiurus quinquestriatus), a substance that evokes neurotransmitter release by depolarizing neurons, was used to activate enteric neurons in short-circuited guinea pig ileum. Scorpion venom increased transmural potential difference and short-circuit current, and this response was similar to the increase that occurred after electrical stimulation of enteric neurons. The stimulus- or venom-evoked response in short-circuit current was abolished by tetrodotoxin. Atropine reduced by 47% the increments in short-circuit current produced by either electrical stimulation or venom. Scorpion venom increased active chloride secretion in short-circuited guinea pig ileal mucosa but had no significant effect on active sodium absorption, residual flux, or total tissue conductance. No morphological changes in transmission electron micrographs of ileal mucosa treated with scorpion venom were evident compared with controls. Alanine caused an increase in short-circuit current in venom-treated tissue that was similar to control values. These results show that scorpion venom mimics the mucosal effects of electrical activation of enteric neurons. These results suggest that a significant component of both scorpion venom action and the response to electrical field stimulation is mediated by neural release of acetylcholine, which activates epithelial muscarinic receptors.     

Neural beta-adrenergic dilatation of the facial vein in man Possible mechanism in emotional blushing

Ring preparations of the superficial buccal segment of the human facial vein, taken from extirpated tissue in 12 patients during neck surgery, were studied in vitro. The vein developed a maintained intrinsic myogenic tone in response to passive stretch and was supplied with α- as well as β-adrenoceptors, both of which could be influenced by transmural nerve stimulation (TNS) and noradrenaline. These unusual characteristics for a vein are basically similar to the ones described for the rabbit facial vein by Pegram, Bevan & Bevan (1976). In man there seemed to be an inter-individual difference with regard to the abundance of ‘innervated’α- and β-adrenoceptors. Facial vein specimens from some subjects thus responded with prompt and pronounced net dilatation to TNS with maximum at 4 Hz and those from others with net constriction with maximum at 16 Hz. The latter showed a reversal into neural β-adrenergic dilatation after α-adrenergic blockade. The human external jugular vein was devoid of intrinsic tone and β-adrenoceptors. It is tentatively proposed that a β-adrenergic neuro-effector mechanism in superficial ramifications of the facial vein in man might be involved in the emotional blushing reaction.     

The effects of calcium and magnesium on inhibitory junctional transmission in smooth muscle of guinea pig small intestine

Summary The membrane potential of smooth muscle cells in the circular layer of the guinea pig ileum was recorded using intracellular electrodes. Transmural stimulation, in the presence of atropine, caused a transient hyperpolarization, an inhibitory junction potential (IJP). IJP's are thought to result from the action of transmitter released from intramural inhibitory nerves. It has been reported that, in the guinea pig jejunum, the amplitude of the IJP resulting from field stimulation is not altered by changes in the calcium and magnesium ion concentration in the bathing solution. Experiments reported here have shown that the IJP amplitude decreased markedly on reducing the calcium ion concentration and or increasing the magnesium ion concentration. Indirect evidence is presented suggesting that the decrease in amplitude of the IJP is due to a decrease in the amount of transmitter released.     

Quercetin inhibits anaphylactic contraction of guinea pig ileum smooth muscle

Certain flavonoids inhibit antigen-induced release of histamine from mast cells and basophils and also inhibit contraction of guinea pig ileum induced by histamine, acetylcholine, and PGE2. We examined the effect of one flavonoid, quercetin, on anaphylactic smooth muscle contraction of ileum from guinea pigs sensitized to egg albumin. Quercetin inhibited both the phasic and tonic components of anaphylactic contraction in a concentration-dependent fashion (IC50 approximately 10 microM). Whether this is primarily an effect on mast cell mediator release or inhibition of mediator effects on smooth muscle has not been established.