The effect of amitriptyline, mianserin, and viloxazine at pre- and post-junctional muscarinic receptors in guinea-pig ileal longitudinal muscle

1982 ◽  
Vol 60 (2) ◽  
pp. 193-200 ◽  
Author(s):  
Y. H. Kwok ◽  
F. Mitchelson
Keyword(s):  
Electrical Stimulation ◽  
Guinea Pig ◽  
Muscarinic Receptors ◽  
Longitudinal Muscle ◽  
Fold Increase ◽  
Selective Inhibition

The antimuscarinic activity of amitriptyline, mianserin, and viloxazine was compared with atropine in guinea-pig ileal longitudinal muscle. The pA2 values obtained using carbachol (CCh) as agonist were as follows: atropine, 9.55; amitriptyline, 7.50; mianserin, 6.40; and viloxazine, 4.91. Responses to transmural electrical stimulation (1–50 Hz) were more resistant than those produced by CCh to inhibition by atropine and the antidepressants. This did not appear to be due to a selective inhibition of prejunctional inhibitory muscarinic receptors, as a pA2 of 8.73 was obtained with atropine for the depression of oxotremorine-induced inhibition of acetylcholine (ACh) output. Amitriptyline (10 μM) caused a 2.4-fold increase in ACh output and was 200-fold weaker than atropine at doubling ACh output in the longitudinal muscle stimulated at 0.3 Hz. Mianserin (10 μM) and viloxazine (1–10 μM) did not significantly affect ACh output. It is suggested that the antidepressants exhibit a greater affinity for the postjunctional muscarinic receptors in the guinea-pig ileal longitudinal muscle.

Investigations into the mechanism of morphine and ethanol inhibition in the guinea pig ileum longitudinal muscle strip

1980 ◽  
Vol 58 (3) ◽  
pp. 265-270 ◽  
Author(s):  
John G. Clement
Keyword(s):  
Guinea Pig ◽  
Muscarinic Receptors ◽  
Longitudinal Muscle ◽  
Opiate Receptor ◽  
Muscle Strip ◽  
Ethanol Inhibition ◽  
Twitch Response ◽  
Mechanism Of Inhibition ◽  
Ethanol Ethanol ◽  
A Site

It has been noted that the analgesic property of ethanol bears a marked resemblance to that of morphine. The purpose of this study was to determine if the mechanism of action of morphine and ethanol was similar using the guinea pig ileal longitudinal muscle strip (GPI-LMS). Ethanol (35–260 mM) depressed the twitch response and the acetylcholine- (ACh-), KCl-, and BaCl2-induced contractions to the same extent while having no significant effect on the binding of [3H]quinuclidinyl benzilate ([3H]QNB) to muscarinic receptors. Morphine (53–530 nM) inhibited the twitch response and to a lesser extent BaCl2- and KCl-induced contractions while having no significant effect on either ACh-induced contractions or the binding of [3H]QNB to muscarinic receptors. Naloxone and increased [Ca2+] reversed the inhibitory effects of morphine but not ethanol. Ethanol appears to inhibit a site after interaction of ACh with the receptor. Mechanism of inhibition of BaCl2 response is also different as naloxone and increased [Ca2+] reverse morphine but not ethanol inhibition. Ethanol inhibition in GPI-LMS does not involve the opiate receptor.

scholarly journals Adenosine as a constituent of the brain and of isolated cerebral tissues, and its relationship to the generation of adenosine 3′:5′-cyclic monophosphate

1977 ◽  
Vol 164 (1) ◽  
pp. 131-137 ◽  
Author(s):  
Michael Newman ◽  
Henry McIlwain
Keyword(s):  
Electrical Stimulation ◽  
Cyclic Amp ◽  
Guinea Pig ◽  
Room Temperature ◽  
Fold Increase ◽  
Electrical Excitation ◽  
Adenosine Concentration ◽  
The Brain ◽  
Guinea Pig Brain

1. Adenosine was determined in rapidly frozen rat and guinea-pig brain and in guinea-pig cerebral tissues after incubation in vitro. Adenosine concentrations were approx. 2nmol/g wet wt. in frozen tissue, diminished at room temperature, and returned to 2nmol/g on incubation in oxygenated glucose/salines. 2. Superfusion with noradrenaline then increased the tissue's adenosine concentration 2.5-fold, and hypoxia caused an 8-fold increase. 3. Electrical stimulation alone or in the presence of noradrenaline or histamine increased the tissue's adenosine and cyclic AMP, but adenosine concentrations reached their peak later and were maintained for longer than those of cyclic AMP. 4. Superfusion with l-glutamate with and without electrical excitation raised adenosine concentrations to 15–34nmol/g. The increases in cyclic AMP on electrical stimulation, superfusion with glutamate or a combination of these treatments were diminished by addition of adenosine deaminase or theophylline. 5. It is concluded that adenosine can be produced endogenously in cerebral systems, in sufficient concentrations to accelerate an adenosine-activated adenylate cyclase, and by this route can contribute to the cerebral actions of electrical stimulation and of the neurohumoral agents. In certain instances cyclic AMP as substrate contributes to an increase in adenosine.

Failure of gallamine and pancuronium to inhibit selectively (−)-[3H]quinuclidinyl benzilate binding in guinea-pig atria

1985 ◽  
Vol 63 (3) ◽  
pp. 200-208 ◽  
Author(s):  
L. K. Choo ◽  
E. Leung ◽  
F. Mitchelson
Keyword(s):  
Guinea Pig ◽  
Muscarinic Receptors ◽  
Binding Sites ◽  
Longitudinal Muscle ◽  
Dependent Manner ◽  
Dose Dependent ◽  
Guinea Pig Atria ◽  
Bimolecular Interaction ◽  
Correlate Data ◽  
Quinuclidinyl Benzilate

Binding of (−)-[3H]quinuclidinyl benzilate (QNB) to muscarinie sites in guinea-pig atrial and ileal longitudinal muscle homogenates showed the presence of a single population of binding sites in atria (KD = 41 (32–53) (95% confidence limits) pM; Bmax = 0.225 ± 0.02 pmol/mg protein (3)) and two binding sites in the ileum (KD = 20.9 (8.8–49) pM and 11.3 nM; Bmax = 0.436 ± 0.09 and 11.85 ± 2.63 pmol/mg protein (4), respectively). Atropine, gallamine, and pancuronium displaced (−)-[3H]QNB binding from the high affinity binding sites in the two tissues in a dose-dependent manner with –log Ki values of 8.6, 6.4, and 6.9, respectively, in atria and 8.7, 6.8, and 6.9, respectively, in ileal longitudinal muscle. The lack of selectivity of gallamine and pancuronium in binding experiments differed from results obtained in isolated tissue experiments where these antagonists showed a marked difference in their ability to antagonize cholinomimetics in the two tissues. In addition, the Ki values for gallamine and pancuronium in ileal homogenates were ca. 130- and 16-fold lower, respectively, than their KB values determined from isolated tissue experiments. Attempts to correlate data from binding experiments and isolated tissue experiments using combinations of antagonists led to variable results attributed to differences in the rates of dissociation of the antagonists from muscarinic receptors. It is concluded that the interaction of gallamine or pancuronium with agonists or antagonists at muscarinic receptors is not a simple bimolecular interaction.

Vagal influence on gastroduodenal HCO3- secretion in the cat in vivo

1987 ◽  
Vol 252 (4) ◽  
pp. G522-G528 ◽  
Author(s):  
O. Nylander ◽  
G. Flemstrom ◽  
D. Delbro ◽  
L. Fandriks
Keyword(s):  
Electrical Stimulation ◽  
Muscarinic Receptors ◽  
Fold Increase ◽  
Vagal Nerves ◽  
Alkaline Secretion ◽  
Gastric Secretions ◽  
Distal Direction ◽  
Vagal Influence

Gastric and duodenal secretions of HCO3- were studied simultaneously in chloralose-anesthetized cats. The adrenals were ligated, and the cervical vagal as well as the abdominal splanchnic nerves were cut. Gastric secretions of H+ and HCO3- were calculated from measurements of the pH and PCO2 in the luminal perfusate. A duodenal segment devoid of Brunner's glands and pancreaticobilary secretions was cannulated in situ and the alkaline secretion determined by continuous titration at luminal pH 7.4. Electrical stimulation in the distal direction for 10–15 min of the cervical vagal nerves resulted in a 6- to 10-fold increase in gastric H+ and in a 20–60% rise in gastric HCO-3 secretion. Duodenal HCO3- secretion increased by 65–155%. Gastric basal secretions of H+ and HCO3- were not affected by atropine or hexamethonium, but both agents inhibited basal duodenal HCO3- secretion. Hexamethonium abolished and atropine reduced the rise in all secretions in response to vagal nerve stimulation. Thus gastroduodenal mucosal HCO3- secretion is stimulated by vagal mechanisms involving action on nicotinic as well as on muscarinic receptors and possibly also noncholinergic neurotransmission.

Selective Inhibition of Thromboxane Synthetase with Dazoxiben - Basis of Its Inhibitory Effect on Platelet Adhesion

1983 ◽  
Vol 49 (02) ◽  
pp. 096-101 ◽  
Author(s):  
V C Menys ◽  
J A Davies
Keyword(s):  
Arachidonic Acid ◽  
Platelet Adhesion ◽  
Fold Increase ◽  
Selective Inhibition ◽  
Inhibitory Effect ◽  
Selective Inhibitor ◽  
Coated Glass ◽  
Thromboxane Synthetase ◽  
Pre Treatment

SummaryPlatelet adhesion to rabbit aortic subendothelium or collagen-coated glass was quantitated in a rotating probe device by uptake of radio-labelled platelets. Under conditions in which aspirin had no effect, dazoxiben, a selective inhibitor of thromboxane synthetase, reduced platelet adhesion to aortic subendothelium by about 40% but did not affect adhesion to collagen-coated glass. Pre-treatment of aortic segments with 15-HPETE, a selective inhibitor of PGI2-synthetase, abolished the inhibitory effect of dazoxiben on adhesion. Concentrations of 6-oxo-PGFlα in the perfusate were raised in the presence of dazoxiben alone, and following addition of thrombin (10 units/ml) there was a 2-3 fold increase in concentration. Perfusion of damaged aorta with platelets labelled with (14C)-arachidonic acid in the presence of thrombin and dazoxiben resulted in the appearance of (14C)-labelled-6-oxo-PGFiα. Inhibition of thromboxane synthetase limits platelet adhesion probably by promoting vascular synthesis of PGI2 from endoperoxides liberated from adherent platelets, which subsequently promotes detachment of cells from the surface.

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