The effect of ion pair formation on the antimuscarinic activity of methantheline.

The quaternary ammonium compound, methantheline, was found to antagonize acetylcholine induced contractions in isolated guinea pig ileum by a mechanism which did not conform to the criteria for either competitive or non-competitive inhibition. Enhancement of the lipid solubility of methantheline by formation of an ion pair with trichloracetate failed to influence its cholinergic inhibitory activity. The results suggest that in the guinea pig ileum a) an intracellular site of action does not exist for methantheline and b) the membrane receptors for methantheline most likely are located in an aqueous environment.     

Tricyclic antidepressants antagonize prostaglandin (PG) E2-induced contractions of the guinea pig ileum and hypomotility in the mouse

The interactions of PGE2 and 2 tricyclic antidepressants were tested both on the guinea pig ileum and motility in the mouse. PGE2-induced contractions of the guinea pig ileum were irreversibly blocked by amitriptyline and desipramine. Chronic administration of amitriptyline and desipramine blocked PGE2-induced hypomotility in the mouse.     

Tricyclic antidepressants antagonize prostaglandin (PG) E20induced contractions of the guinea pig ileum and hypomotility in the mouse

Summary The interactions of PGE₂ and 2 tricyclic antidepressants were tested both on the guinea pig ileum and motility in the mouse. PGE₂-induced contractions of the guinea pig ileum were irreversibly blocked by amitriptyline and desipramine. Chronic administration of amitriptyline and desipramine blocked PGE₂-induced hypomotility in the mouse.     

Effects of a new cholecystokinin antagonist (GE 410) on the smooth muscle of the guinea pig ileum

Suc-Tyr-(SE)-Met-Gly-Trp-Met-Asp-beta-phenethylamide (GE 410) competitively antagonized the contractions of smooth muscle strips from guinea pig ileum (pA2 = 7.6, n = 0.95) induced by cholecystokinin-octapeptide (CCK8). GE 410 inhibited the electrically-induced cholinergically mediated contractile responses and the [3H]ACh release in the ileum, as well as the CCK-stimulated electrical contractile responses and the [3H]ACh release in the cholinergic nerve terminals. The results suggest the existence of CCK-receptors not only in the smooth muscles but also on the neurons.     

Nerve-mediated action of forskolin on guinea pig ileal mucosa

The effects of forskolin on myenteric neuronal activity and mucosal function were examined in guinea pig ileum. Forskolin increased the excitability of myenteric neurons, and increased mucosal chloride secretion by stimulating enteric neurons as well as by acting directly on enterocytes.     

Effects of a new cholecystokinin antagonist (GE 410) on the smooth muscle of the guinea pig ileum

Summary Suc-Tyr-(SE)-Met-Gly-Trp-Met-Asp--phenethylamide (GE 410) competitively antagonized the contractions of smooth muscle strips from guinea pig ileum (pA₂=7.6, n=0.95) induced by cholecystokinin-octapeptide (CCK8). GE 410 inhibited the electrically-induced cholinergically mediated contractile responses and the [³H]ACh release in the ileum, as well as the CCK-stimulated electrical contractile responses and the [³H]ACh release in the cholinergic nerve terminals. The results suggest the existence of CCK-receptors not only in the smooth muscles but also on the neurons.     

Failure of coffee to inhibit the pharmacodynamic activity of morphine in vivo

High doses of caffeine-containing as well as decaffeinated instant coffee neither inhibited morphine-induced analgesia in mice nor the morphine-induced fall of blood pressure, heart rate and respiratory rate in rats. On the contrary, caffeine-containing coffee even enhanced the analgesic effects of morphine in mice. Coffee thus does not exhibit opiate-antagonizing activity in the whole organism in vivo. The very weak morphine-antagonistic efficacy of coffee powder in the myenteric plexus-longitudinal muscle preparation from the guinea pig ileum is of no practical importance.     

Nerve-mediated action of forskolin on guinea pig ileal mucosa

Summary The effects of forskolin on myenteric neuronal activity and mucosal function were examined in guinea pig ileum. Forskolin increased the excitability of myenteric neurons, and increased mucosal chloride secretion by stimulating enteric neurons as well as by acting directly on enterocytes.Acknowledgment. The authors thank E. Martens, S. Bowen for technical assistance and N. Schaad for secretarial assistance. This work was supported by National Institutes of Health Grants, F32-AM07301, K-104-AM1004, RO1-AM29699, RO1-AM26742 and an Eloise Gerry Fellowship.     

Versuche zur chromatographischen Trennung der im Augenstiel vonAstacus astacus enthaltenen myotropen Wirkstoffe

Summary The detection of two myotropic substances in the eyestalk and the brain of the crayfishAstacus astacus and the shrimpCrangon crangon was described². Both substances have an action on the isolated ileum of the guinea pig. The substance extracted from the eyestalk has a positive myotropic one, the substance extracted from the brain an inhibiting one.Further a method is given for the separation and purification of the positive myotropic substance of the eyestalk by paper-chromatography.     

Failure of coffee to inhibit the pharmacodynamic activity of morphine in vivo

Summary High doses of caffeine-containing as well as decaffeinated instant coffee neither inhibited morphine-induced analgesia in mice nor the morphine-induced fall of blood pressure, heart rate and respiratory rate in rats. On the contrary, caffeine-containing coffee even enhanced the analgesic effects of morphine in mice. Coffee thus does not exhibit opiate-antagonizing activity in the whole organism in vivo. The very weak morphine-antagonistic efficacy of coffee powder in the myenteric plexus-longitudinal muscle preparation from the guinea pig ileum is of no practical importance.     

Prostaglandin-like substances inPropionibacterium acnes. V. Activity profiles using cascade superfusion bioassay and platelet aggregation

Summary The activity spectrum of prostaglandin-like substances (PLS) fromP. acnes was investigated with cascade superfusion technique and by platelet aggregation assay. The biological activity of PLS resembles that of PGI₂: both relax bovine coronary artery, rabbit mesentric and coeliac arteries; both contract the rat stomach strip as well as both typically inhibit spontaneous movements of isolated guinea pig ileum. Also, similarly to PGI₂, PLS inhibits platelet aggregation regardless the inducer used. However, PLS possesses a specific antiaggregatory pattern on platelet, which indicates that these compounds are not indentical with primary prostaglandins or PGI₂.     

Action of toxins isolated from scorpion and sea anemone venoms on ileum isolated from reserpine-treated guinea pigs]

We have shown that the ileum isolated from a reserpinized guinea Pig does respond to toxin II obtained from Scorpion venom but does not react to Anemonia sulcata toxin. We conclude that if Acetylcholine is the neurotransmitter inducing pharmacological activity of Scorpion toxin it is serotonin which triggers activity of Anemonia sulcata toxin in ileum of a normal guinea Pig.     

Activation of complement by trypanosomes

Summary Factors exhibiting anti-complementary activity released from trypanosomes after incubation at 20°C were described. The active material was shown to consume the first component of bovine complement. While the anticomplementary factor(s) from T. lewisi could activate bovine, human and guinea pig complement, the factor(s) from T. congolense was observed to activate bovine complement, but not guinea pig and only slightly human complement. The roles of complement activating factor(s) of trypanosomes in the pathology of the disease are discussed.This project is supported by National Research Council of Canada grant A 0068 and a grant from the International Development Research Centre.     

Activation of complement by trypanosomes.

Factors exhibiting anti-complementary activity released from trypanosomes after incubation at 20 degrees C were described. The active material was shown to consume the first component of bovine complement. While the anti-complementary factor(s) from T. lewisi could activate bovine, human and guinea pig complement, the factor(s) from T. congolense was observed to activate bovine complement, but not guinea pig and only slightly human complement. The roles of complement activating factor(s) of trypanosomes in the pathology of the disease are discussed.     

Tetrodotoxin slightly shortens action potential duration in ventricular but not in atrial heart muscle

Tetrodotoxin (TTX), at concentrations significantly decreasing maximal upstroke velocity (dV/dtmax) of the action potential, exerted variable effects on action potential duration (APD) in different myocardial preparations. APD was virtually unchanged by tetrodotoxin in the guinea pig atrium, but slightly shortened in the guinea pig ventricle at maximally effective concentrations. In the human ventricle, both dV/dtmax and APD were reduced in the same concentration range of TTX. These results suggest that a TTX-sensitive sodium current significantly contributes to the repolarization phase of the action potential in ventricular but not in atrial heart muscle.     

Enclomiphene induces luteolysis in the nonpregnant guinea pig

The effect of two antiestrogens, enclomiphene and tamoxifen, on luteal function in the guinea pig was compared to that of estradiol, a known luteolysin. Enclomiphene caused premature luteolysis when administered during the early or mid-luteal phase of the cycle, but was not as potent as estradiol. Tamoxifen had no effect. The luteolytic effect of enclomiphene was mediated by the uterus, as has been shown for estradiol.     

Enclomiphene induces luteolysis in the nonpregnant guinea pig

Summary The effect of two antiestrogens, enclomiphene and tamoxifen, on luteal function in the guinea pig was compared to that of estradiol, a known luteolysin. Enclomiphene caused premature luteolysis when administered during the early or mid-luteal phase of the cycle, but was not as potent as estradiol. Tamoxifen had no effect. The luteolytic effect of enclomiphene was mediated by the uterus, as has been shown for estradiol.     

Tetrodotoxin slightly shortens action potential duration in ventricular but not in atrial heart muscle

Summary Tetrodotoxin (TTX), at concentrations significantly decreasing maximal upstroke velocity (dV/dt_max) of the action potential, exerted variable effects on action potential duration (APD) in different myocardial preparations. APD was virtually unchanged by tetrodotoxin in the guinea pig atrium, but slightly shortened in the guinea pig ventricle at maximally effective concentrations. In the human ventricle, both dV/dt_max and APD were reduced in the same concentration range of TTX. These results suggest that a TTX-sensitive sodium current significantly contributes to the repolarization phase of the action potential in ventricular but not in atrial heart muscle.Supported by the Deutsche Forschungsgemeinschaft (Na 105/5-5) and by the Fonds der Chemischen Industrie. Author to whom reprint requests should be addressed. We thank Mrs. Johanna Rupp for expert technical help. We also thank one referee for suggesting the experiments depicted in figure 4.     

Production of active and passive anaphylactic shock in the WBB6F1 mouse, a mast cell-deficient strain

The role of mast cells in active and passive anaphylactic shock was examined using the WBB6F1 mouse, a genetically mast cell-deficient strain. Lethal anaphylactic shock occurred at high incidence rates in mice actively sensitized to bovine serum albumin (BSA). The reaction was specific to BSA since the shock could not be elicited by human or guinea pig serum albumin in these animals. Lethal shock could be prevented by CV-3988 but not by cyproheptadine, which suggests that the shock is mediated by PAF but not by histamine and serotonin. Similarly, lethal shock was provoked by homologous antigens in mice which had been passively sensitized with allogeneic anti-benzylpenicilloyl (BPO) IgG1 monoclonal antibody or with allogeneic or xenogeneic anti-BSA antiserum, but not in those sensitized with allogeneic anti-BPO IgE monoclonal antibody. These findings suggest that mast cells are not necessarily required for anaphylactic shock in the mouse.     

Calyculin A increases voltage-dependent inward current in smooth muscle cells isolated from guinea pig taenia coli.

The effects of a potent phosphatase inhibitor, calyculin A (CL-A), on inward currents in guinea pig taenia coli smooth muscle cells were examined. CL-A increased the inward current, and this effect of CL-A was inhibited by a protein kinase C inhibitor, H-7, and by nifedipine. Phorbol 12,13-dibutyrate, an activator of protein kinase C, also increased the inward current and this effect was antagonized by H-7. These results suggest that in guinea pig taenia coli smooth muscle cells CL-A may facilitate the opening of the L-type Ca2+ channels through the protein kinase C-dependent phosphorylation system.