Effects of pinacidil on guinea-pig airway smooth muscle contracted by asthma mediators

Pinacidil is a new antihypertensive, direct vasodilator drug which has been classified as a K+ channel opener. The present study demonstrated a concentration-dependent relaxant activity of pinacidil in guinea-pig tracheal preparations. The potency and efficacy of pinacidil depended on the agent used to induce tracheal tone. Tracheal preparations with spontaneous tone or precontracted by different asthma mediators were completely relaxed by pinacidil. A high potency was found in spontaneously contracted preparations (EC50 = 7.8 x 10(-7) M). The EC50 values ranged from 2.3 to 5.4 x 10(-6) M in histamine-, PGF2 alpha- or LTC4-contracted preparations. When tone was induced by carbachol, the EC50 was 2.1 x 10(-5) M. In contrast, pinacidil produced incomplete relaxation and had a low potency in preparations contracted by 30 or 124 mM K+ Krebs solutions. This effect profile differed from that seen with beta 2-receptor agonists, xanthines and Ca2+ antagonists in guinea-pig trachealis and seems compatible with K+ channel opening as a primary mode of relaxation for pinacidil in airway smooth muscle.     

重组人白细胞介素-1受体拮抗药对豚鼠离体呼吸道平滑肌的影响

目的　观察人重组白细胞介素 1受体拮抗剂 (IL 1ra)对正常和卵白蛋白致敏豚鼠离体肺条、气管平滑肌的影响。方法　应用离体器官装置、张力换能器、MedLab记录系统测定肺条和气管平滑肌的张力。结果　①IL 1ra对正常豚鼠离体肺条和气管平滑肌有直接松弛作用 ,EC50 分别为1 2 9ⅹ 10 -7mol·L-1和 8 0 6× 10 -8mol·L-1;并对卵白蛋白致敏的豚鼠肺条和气管平滑肌也有直接的松弛作用 ,EC50 分别为 2 6 1× 10 -7mol·L-1和 5 88× 10 -7mol·L-1,但致敏豚鼠呼吸道平滑肌对IL 1ra的敏感性要比正常豚鼠低。②IL 1ra(10 -9～ 10 -5mol·L-1)可剂量依赖性地抑制致痉剂组胺对正常豚鼠肺条和气管平滑肌的收缩作用 (P <0 0 1)。③IL 1ra能抑制卵白蛋白攻击引起的肺条和气管平滑肌的收缩 ,IC50 分别为 7 83ⅹ 10 -7mol·L-1和 4 4 8ⅹ 10 -7mol·L-1。结论　IL 1ra对正常、痉挛及致敏状态的呼吸道平滑肌均有松弛作用     

Effects of novel pyridothiazepines and pyridothiazines on contractility of isolated guinea-pig heart muscle and vascular smooth muscle preparations.

The effects of newly synthesized pyridothiazepines MM 4 (1-[N-[2-(3,4-dimethoxy-phenyl)ethyl]-N-methylaminoacetyl]-1,2,3,4 -tetrahydro-pyrido[2,3-b][1,4]thiazepine fumarate), MM 6 (1-[N-[2-(3,4-dimethoxyphenyl)-ethyl]-N-methylaminopropionyl]-1,2, 3,4-tetrahydro-pyrido[2,3-b][1,4]thiazepine fumarate) and the novel pyridothiazines MM 10 (2,3-dihydro-1-[N-[2-(3,4-dimethoxyphenyl)ethyl]-N-methylaminoacetyl+ ++]-1H-pyrido[2,3-b][1,4]thiazine fumarate) and MM 11 (2,3-dihydro-1-[N-[2-(3,4-dimethoxy-phenyl)ethyl]-N-methylaminopropio nyl]-1H-pyrido[2,3-b][1,4]thiazine fumarate) on the contractility of isolated papillary muscles and aortic preparations of guinea pigs were studied using isometric contraction force measurements. The EC50 values for the negative inotropic effect were 27 micromol/l (MM 4), 19 micromol/l (MM 6), 32 micromol/l (MM 10) and 24 micromol/l (MM 11). In K+-precontracted aortic rings ([K+]o 60 mmol/l), the compounds induced relaxation with EC50 values of 27 micromol/l (MM 4), 24 micromol/l (MM 6), 84 micromol/l (MM 10) and 68 micromol/l (MM 11). Pyridothiazepines as well as pyridothiazines (100 micromol/l) were able to depress norepinephrine bitartrate (NE 10 micromol/l)-induced contraction of aortic rings in a calcium-free solution. It was concluded that the investigated compounds exert calcium antagonistic properties in both cardiac and smooth muscle. This antagonistic effect might be due to the inhibition of transmembrane calcium influx and/or intracellular calcium release.     

Enhancement by prostacyclin of the contractility of the guinea-pig airways smooth muscle

Aerosolized prostacyclin (PGI2) potentiated the increase in pulmonary resistance to inflation induced by serotonin, prostaglandin F2 alpha (PGF2 alpha), acetylcholine and histamine in the guinea-pig. This was not due to a reflex, nor to further production of PG cyclooxygenase derivatives. PGI2 and PGF2 alpha induced contraction of the parenchyma lung strip of the guinea-pig, which could be inhibited by polyphloretin phosphate and by PGE1. Since PGF2 alpha failed to potentiate the bronchial responses to acetylcholine, histamine or serotonin, under conditions where PGI2 was effective, the in vitro similarities between the two PGs cannot explain the in vivo results. The ability of PGI2 to potentiate bronchial responses was not shared by the other PGs. Since the latter are either bronchoconstrictor agents by themselves (PGF2 alpha and PGD2), or bronchodilators (PGE1, PGE2), our hypothesis is that PGI2 potentiates the responses of the bronchi to various agonists by a mechanism similar to that which accounts for the potentiation of acute inflammation and pain by PGE1 and PGE2, the latter being ineffective in enhancing the bronchial responses because of the associated bronchodilator activity.     

Does naloxone induce relaxation of guinea-pig airway smooth muscle?

The effects of the opiate receptor antagonist naloxone were investigated on isolated preparations of guinea-pig trachealis contracted with either histamine, methacholine or KCl. The commercially available solution of naloxone (Narcan) induced concentration-dependent relaxation of the contracted airway preparations. In stark contrast, aqueous solutions of naloxone were without any significant relaxant effect. Aqueous solutions of the preservatives (methyl and propyl hydroxybenzoate) present in the vehicle used in the commercial formulation of naloxone mimicked exactly the relaxant effects induced by Narcan. Thus, naloxone does not directly induce relaxation of airway smooth muscle. The effects of Narcan can be solely attributed to the activity of the preservatives present in the vehicles. The mechanism underlying the bronchodilator activity of methyl and propyl hydroxybenzoate is unknown but is not related to receptor blockade or to alterations in the intracellular levels of cyclic AMP.     

The effect of airway epithelium on smooth muscle contractility in bovine trachea.

In bovine tracheal smooth muscle the presence of airway epithelium significantly reduced the sensitivity and maximum contractile response to histamine, 5-hydroxytryptamine (5-HT) or acetylcholine. Muscle contraction induced by K+ and electrical field stimulation was of similar magnitude both in the presence or absence of adherent epithelium. The effect of epithelium on smooth muscle contractility was unaffected by pretreatment with indomethacin (10(-6) M) or mepacrine (5 X 10(-5) M). The relaxant response to isoprenaline was enhanced in the presence of epithelium, although this was significant only in the case of precontraction with 5-HT. It is concluded that the bronchial epithelium may produce a relaxant factor which is not a cyclooxygenase or lipoxygenase product. The production of this factor may be reduced or lost following epithelial damage and this may be important in the pathogenesis of bronchial hyperresponsiveness in asthma.     

Effects of 3,3'-di-O-methylquercetin on guinea-pig isolated smooth muscle

The effects of the flavone 3,3'-di-O-methylquercetin (DOMQ) have been examined and compared with those of quercetin, on guinea-pig isolated ileum, trachea, and main pulmonary artery (MPA). Except for transient contractions induced by low concentrations (10(-8)-3 x 10(-6) M), DOMQ and quercetin (up to 3 x 10(-4) M) caused reduction of the tone and the phasic contractions of the ileum. A23187 reversed the inhibitory effects of quercetin but not those of DOMQ. DOMQ and quercetin caused concentration-dependent relaxation of the trachea and the adrenaline-contracted MPA. DOMQ shifted to the right the concentration-effect curves induced by acetylcholine on the ileum and the trachea, and by adrenaline on MPA and those induced by CaCl2 on ileum, trachea and MPA. DOMQ also inhibited the contractions induced, in Ca2+-free EGTA-containing buffer, by histamine on ileum and by adrenaline on MPA. These observations suggest that DOMQ inhibits Ca2+ influx, Ca2+ release from intracellular stores and, more likely, Ca2+ binding to intracellular receptor proteins.     

Corticosteroid modulation of Na(+)-K+ pump-mediated relaxation in maturing airway smooth muscle.

1. The ontogeny of the relaxant influence of the airway electrogenic Na(+)-K+ pump and its potential modulation by corticosteroids were examined in airway smooth muscle (ASM) segments isolated from newborn and adult rabbits. 2. Control and methylprednisolone-treated (MP) ASM segments were half-maximally contracted with methacholine in K(+)-free buffer and the ASM relaxant responses to Na(+)-K+ pump activation were subsequently evaluated. Relative to adult ASM, control newborn ASM showed significantly enhanced maximal relaxation (Rmax) to KCl (62.5 +/- 5.2% vs. 47.8 +/- 5.2%), but no difference in sensitivity (pC2 = -log concentration producing 50% Rmax: 2.18 +/- 0.12 vs. 2.29 +/- 0.09-log M). 3. Exposure of ASM segments to 500 microM methylprednisolone for 1 h potentiated the airway Na(+)-K+ pump activity. A more pronounced effect was obtained in newborn ASM, where both the Rmax and pC2 values were significantly enhanced. In mature ASM, only the Rmax response to KCl was increased in the presence of MP. 4. Collectively, these data demonstrate that: (i) the functional activity of the airway electrogenic Na(+)-K+ pump decreases with post-natal maturation in the rabbit: (ii) corticosteroid treatment potentiates Na(+)-K+ pump activity in rabbit ASM; and (iii) the latter effect of corticosteroids is enhanced in immature airways. 5. The above findings provide new evidence that the airway relaxant response to activation of the electrogenic Na(+)-K+ pump varies ontogenetically and that corticosteroids potentiate the Na(+)-K+ pump activity in an age-dependent manner.     

Action of the Na ionophore monensin on vascular smooth muscle of guinea-pig aorta

The effects of the Na⁺ ionophore monensin on contractile responses were investigated in guinea-pig aorta in normal and high K⁺ solutions. In normal K⁺ (5.4 mM) solution, monensin (2 × 10⁻⁵ M) produced a rapid increase in tension followed by slow relaxation. This contraction was markedly inhibited by phentolamine (10⁻⁵ M) or prazosin (10⁻⁶ M) and was accompanied by an increase in tritium efflux from tissue preloaded with [³H]norepinephrine. In the presence of phentolamine, monensin (1–2 × 10⁻⁵ M) or ouabain (1−2 × 10⁻⁵ M) caused only a small and slowly developing contraction. Simultaneous application of these agents caused a more rapid and greater contraction. Either monensin or ouabain gradually increased cellular Na⁺ and decreased cellular K⁺ content. When monensin was applied simultaneously with ouabain, there was a rapid increase in cellular Na⁺ and loss of cellular K⁺. In high K⁺ (65.4 mM) solution, monensin (10⁻⁶ M) slightly reduced the increased tension level but when external glucose was omitted monensin markedly inhibited the contraction. A significant decrease in tissue ATP content was observed only when monensin was applied in glucose-free solution. Similarly, hypoxia (N₂ bubbling) markedly inhibited the high K⁺ contraction and decreased the tissue ATP content only in the absence of glucose. These results suggest that monensin produces a neurogenic contraction due to the release of endogenous catecholamines and also produces a myogenic contraction by a decrease in transmembrane Na⁺ and K⁺ gradients when the Na⁺ and -K⁺ pump is inhibited by ouabain, and that monensin inhibits aerobic energy metabolism of vascular smooth muscle.     

Effects of vasopressin on smooth muscle cells of guinea-pig mesenteric vessels

1 The effects of vasopressin on the membrane and contractile properties of smooth muscle cells of guinea-pig mesenteric arteries, and mesenteric and portal veins were investigated in various ionic environments by means of a micro-electrode technique and an isometric tension recording method. The results were compared with those obtained with oxytocin and noradrenaline (NA).     

Relationship between stimulated inositol lipid hydrolysis and contractility in guinea-pig visceral longitudinal smooth muscle

Carbamylcholine caused a marked, concentration-dependent stimulation of [3H]Ins P, [3H] InsP2 and to a lesser extent [3H]InsP3 production in guinea-pig longitudinal smooth muscle prelabelled with myo-[3H]inositol. Accumulation of these three inositol phosphates showed differential sensitivity to LiCl. Muscle contraction was apparent at lower concentrations of carbamylcholine. Both responses were mediated via muscarinic-type receptors. An association of inositol phosphate production and contractility was also observed in response to substance P, histamine and noradrenaline, the latter via an alpha-adrenergic mechanism. The Ca2+-channel agonist CGP 28392 failed to stimulate inositol phosphate production despite inducing a contractile response. Carbamylcholine -induced inositol phosphate production persisted in the presence of D600 or Mn2+ despite loss of contractile activity. However, both responses showed a similar, marked dependence on the presence of Ca2+ in the extracellular medium. Mn2+ could restore basal and stimulated inositol phosphate production in low Ca2+ solutions but could not substitute for Ca2+ in restoring contractility. The results suggest that stimulated inositol lipid hydrolysis in longitudinal smooth muscle does not result from Ca2+ entry into the tissue, although the response does depend on the concentration of divalent cations in the extracellular medium. This dependency may be related to the maintenance of membrane potential and possibly phospholipid conformation.     

Effects of dichloroglyoxime on isolated guinea-pig smooth muscle and atrium.

The effects of dichloroglyoxime (DCG) on isolated rings of aorta, main pulmonary artery, trachea and spontaneously-beating atrium of guines-pig were studied. DCG caused concentration- dependent relaxation of the epinephrine-contracted aortic and pulmonary artery rings and of the tone of tracheal rings. Propranolol caused a slight shift to the right in the concentration-effect curves of DCG on these preparations. Quinacrine, an inhibitor of the release of arachidonic acid and its metabolites, caused a significant shift to the right in the concentration-effect curves of DCG on the three preparations. Low concentrations of DCG increased the beating rate of the atrium, an effect which was blocked by propranolol but not by quinacrine whereas large concentrations decreased the beating rate, an effect which was not significantly affected by propranolol or by quinacrine. DCG also caused a concentration-dependent decrease in the contractility of the atrium and this effect was only slightly affected by propranolol or quinacrine. These observations suggest that the relaxant effect of dichloroglyoxime on the smooth muscle may not be mediated by the stimulation of beta adrenoceptors specifically although a nonspecific interaction with these receptors or with the contractile machinery of the cell cannot be excluded. Data with quinacrine suggest that the effects may be mediated by the release of an inhibitory metabolite of arachidonic acid. The results further suggest that in the atrium the effects of DCG may not be specific and they may be partially mediated by the release of catecholamines from the nerve endings.     

Calcium regulation of smooth muscle contractility

Simultaneous measurements of cytoplasmic Ca2+ level [( Ca2+]i) and muscle contraction in smooth muscle indicated that [Ca2+]i gradually decreases during sustained contraction. This time-dependent dissociation has been explained by the latch bridge hypothesis, positive cooperativity between phosphorylated and non-phosphorylated crossbridges, involvement of cytoskeleton phosphorylation, or connection between myosin and actin filaments by caldesmon. Furthermore, it has been found that receptor agonists induce greater contraction than high K+ for a given increase in [Ca2+]i. This stimulus-dependent dissociation may be due to the receptor agonists-induced activation of protein kinase C which in turn decreases the inhibitory effect of calponin on the actin-myosin interaction, resulting in an apparent Ca2+ sensitization. Thus, the contractions induced by receptor agonists are due not only to the increase in [Ca2+]i but also to the increase in Ca2+ sensitivity of contractile elements. Ca2+ channel blockers inhibit the increase in [Ca2+]i but not the Ca2+ sensitization, and this may be the reason why these blockers are relatively weak inhibitors of the contraction induced by receptor agonists. By contrast, cyclic AMP and cyclic GMP decrease the Ca2+ sensitivity of contractile elements in addition to their effects to decrease [Ca2+]i.     

Protective effects of anisodamine on cigarette smoke extract-induced airway smooth muscle cell proliferation and tracheal contractility

Anisodamine, an antagonist of muscarinic acetylcholine receptors (mAChRs), has been used therapeutically to improve smooth muscle function, including microvascular, intestinal and airway spasms. Our previous studies have revealed that airway hyper-reactivity could be prevented by anisodamine. However, whether anisodamine prevents smoking-induced airway smooth muscle (ASM) cell proliferation remained unclear. In this study, a primary culture of rat ASM cells was used to evaluate an ASM phenotype through the ability of the cells to proliferate and express contractile proteins in response to cigarette smoke extract (CSE) and intervention of anisodamine. Our results showed that CSE resulted in an increase in cyclin D1 expression concomitant with the G0/G1-to-S phase transition, and high expression of M2 and M3. Functional studies showed that tracheal hyper-contractility accompanied contractile marker α-SMA high-expression. These changes, which occur only after CSE stimulation, were prevented and reversed by anisodamine, and CSE-induced cyclin D1 expression was significantly inhibited by anisodamine and the specific inhibitor U0126, BAY11-7082 and LY294002. Thus, we concluded that the protective and reversal effects and mechanism of anisodamine on CSE-induced events might involve, at least partially, the ERK, Akt and NF-κB signaling pathways associated with cyclin D1 via mAChRs. Our study validated that anisodamine intervention on ASM cells may contribute to anti-remodeling properties other than bronchodilation.     

Alteration of smooth muscle contractility after muscarinic agonist-induced K+ loss.

1. After stimulation of the longitudinal smooth muscle of the guinea-pig ileum by an optimal dose (2 x 10(-7) M) of a muscarinic agent, cis-2-methyl-4-dimethylaminomethyl-1,3-dioxolane methiodide (CD), the muscles failed to regain their normal spontaneous activity for 20 to 30 min. During the recovery period, subsequent contractions induced by either CD or 60 mM KCl were altered, particularly when only short times (15 min or less) were allowed between exposures. 2. Altered responses to CD had depressed phasic but increased tonic tensions and were characteristic of responses induced by lower doses of CD. The altered responsiveness probably represented an early phase of muscle 'densensitization'. 3. In contrast to muscarinic stimulation, the smooth muscles gave identical responses after repeated stimulation by 60 mM KCl, even when only 2 min were allowed between exposures. 4. Whereas K+ levels increased in muscles exposed to 60 mM KCl, they decreased during contractions to CD. The K+ levels remained low until the muscles recovered their normal responsiveness. 5. Increasing the extracellular K+ concentration (5 to 13 mM) hastened the recovery of the muscle responsiveness after CD, whereas lowering external K+ concentration to 1.35 mM or the addition of ouabain (5 x 10(-7) M) delayed the recovery. The results suggested that the Na+, K+-pump is rate-limiting in the recovery of the normal ionic balance of the muscles after stimulation by muscarinic agonists.     

Role of human airway smooth muscle in altered extracellular matrix production in asthma

1. The underlying abnormality in asthma is not fully understood; however, inflammation, airway remodelling and bronchial hyperresponsiveness are key factors. The plasma exudate from the microvascular leakage plays a significant role in remodelling, which includes extracellular matrix (ECM) protein deposition/breakdown and airway smooth muscle (ASM) hyperplasia/hypertrophy. 2. The ECM is an intricate network of macromolecules that forms the 'scaffolding' of the airways. This scaffolding not only acts as mechanical support that plays a crucial role in the maintenance of airway function and structure, but it is also a dynamic and complex network that has the potential to influence cellular function, including migration, differentiation and proliferation of a number of cell types. 3. In asthmatic airways, the profile of ECM proteins is altered. The deposition of collagen I, III, V, fibronectin, tenascin, hyaluronan, versican and laminin alpha2/beta2 is increased, whereas the deposition of collagen IV and elastin is decreased. 4. This imbalance in the ECM profile within the asthmatic airway could be due to: (i) increased de novo synthesis of ECM proteins; (ii) decreased activity of its degrading enzymes, namely matrix metalloproteinases (MMP); or (iii) upregulation of the tissue-specific inhibitors of metalloproteinases (TIMP). 5. One of the characteristic features of asthma is an increase in the amount of ASM within the airways. The ECM proteins/MMP/TIMP in and around the smooth muscle may play a contributory role in this increased growth. 6. The role of current asthma treatments in the prevention or reversal of airway ECM changes is an area that has only recently become of interest, with the majority of the in vivo work focusing on the effects of corticosteroids. 7. The evidence presented in this review indicates that the ASM may influence its own environment/proliferation through the production of ECM proteins, MMP and TIMP. Further studies are needed to fully understand the role of the ASM in the production of ECM proteins, MMP and TIMP andtheir potential influence in the mechanisms underlying asthma.     

Effects of cromakalim on neurally-mediated responses of guinea-pig tracheal smooth muscle.

1. The ability of cromakalim to modulate several different types of neuroeffector transmission has been assessed in guinea-pig isolated trachea. 2. In trachea treated with propranolol (10(-6) M) and indomethacin (2.8 x 10(-6) M), stimulation of the extrinsic vagal nerves evoked contractions which were blocked by hexamethonium (5 x 10(-4) M) or by tetrodotoxin (TTX; 10(-6) M). Cromakalim (10(-5) M) caused a two fold rightward shift of the frequency-response curve. 3. In carinal trachea treated with propranolol and indomethacin, transmural stimulation evoked an initial, rapid contraction followed by a more sustained secondary contraction. The initial, rapid contractile response was virtually ablated by atropine (10(-6) M) or by TTX but was resistant to hexamethonium. Cromakalim (10(-8)-10(-5) M) caused a concentration-dependent rightward shift of the frequency-response curve for the initial contraction. 4. In carinal trachea treated with atropine, propranolol and indomethacin, transmural stimulation evoked only the secondary (non-adrenergic, non-cholinergic (NANC] contractile responses. These were markedly reduced by TTX but were resistant to hexamethonium. Cromakalim (10(-8)-10(-5) M) suppressed the NANC contractile responses in a concentration-dependent manner. This action could be offset by glibenclamide (10(-6) M). 5. In trachea treated with atropine, histamine (10(-4) M), propranolol and indomethacin, transmural stimulation evoked NANC relaxant responses. Cromakalim (up to 10(-5) M) was without effect on the frequency-response curve for the stimulation of NANC inhibitory nerves. 6. Tested on trachea bathed by drug-free Krebs solution, cromakalim (10(-7)-10(-5) M) caused concentration-dependent suppression of tracheal tone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of new 4-aminopyridine derivatives on neuromuscular transmission and on smooth muscle contractility

The effects of new 4-aminopyridine (4-AP) derivatives were investigated in the isolated mouse phrenic nerve-hemidiaphragm preparation under single impulse stimulation and tetanic conditions. The basic 4-AP structure was modified in position 3 on the pyridine nucleus by introducing different substituents. Results were compared to those obtained with 4-AP and 3,4-diaminopyridine. The compounds were tested for their antagonistic effect against calcium antagonists and botulinum toxin A. The effect on smooth muscle was investigated on the isolated guinea-pig ileum. Physico-chemical parameters of the test compounds were determined by the partition coefficient and ionization constant. Finally structure-activity relationship analysis revealed that the activity was highly related to lipophilicity and the steric volume. So far 4-AP itself provided the most advantageous molecular structure.     

Palytoxin-induced K+ efflux from ileal longitudinal smooth muscle of the guinea-pig

In guinea-pig ileal longitudinal smooth muscle, both palytoxin (PTX) and carbachol (CCh) increased K+ efflux with an EC50 of 1.8 X 10(-10) M and 4.1 X 10(-7) M, respectively. Atropine (10(-6) M) did not inhibit the K+ efflux due to PTX (3 X 10(-9) M), but completely inhibited the efflux due to CCh (10(-5) M). External Ca2+ removal and verapamil (10(-5) M) did not change the PTX-induced K+ efflux, although the CCh-induced K+ efflux was inhibited about 77% and 71%, respectively. PTX-induced K+ efflux was reduced to 31% by a depletion of intracellular Ca2+. Tetraethylammonium (15 mM) inhibited the K+ efflux due to PTX or CCh to 61% or 75%, respectively. The PTX-induced K+ efflux was also inhibited by cymarin (3 X 10(-8) M), ouabain (10(-5) M) and digitoxin (10(-5) M). These results suggest that the PTX-induced K+ efflux is less dependent on Ca2+ influx than that due to CCh. Furthermore, the binding sites for PTX in the ileal muscle of guinea-pig may be Na+, K+-ATPase, as has been suggested in other types of cells.     

Modification of smooth muscle contractility by Cordemcura

Cordemcura causes a dose-dependent inhibition of noradrenaline contractions of isolated rabbit aorta as well as of isolated guinea pig ductus deferens. In both organ preparations analogous intensity of effect has been observed. In different intestinal isolated organs Cordemcura also produces a dose-dependent inhibition against different agonists. The Ba2+-induced contraction is inhibited to approximately the same extent as various receptor-induced contractions. Consequently a specific receptor function on smooth muscle has to be excluded with regard to Cordemcura. Furthermore Cordemcura has a bronchodilatory effect. This property could be proved by the protection effect as observed in the inhalative histamine-induced bronchoconstriction in guinea pig.