Further characterization of the putative 5-HT4 receptor mediating depolarization of the rat isolated vagus nerve.
A putative 5-HT4 receptor-mediated depolarization of the rat isolated vagus nerve has been studied using a grease-gap extracellular recording technique. Ondansetron (1 microM) was used to block the predominant 5-HT3 receptor mediated depolarization in this preparation and the effects of the 5-HT4 receptor antagonists DAU 6285 (endo-8-methyl-8-azabicyclo [3.2.1] oct-3-yl-2,3-dihydro-6-methoxy-2-oxo-1H-benzimidazole-1- carboxylate HCl); 0.3, 1.0 or 3.0 microM and SDZ 205-557 (2-methoxy-4-amino-5-chloro-benzoic acid 2-(diethylamino)-ethyl ester HCl); 0.1, 0.3 or 1.0 microM were studied on the residual, ondansetron-resistant, component of the response. The effects of the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) and of forskolin on the ondansetron-resistant response were also studied. Both DAU 6285 and SDZ 205-557 acted as competitive antagonists of the ondansetron-resistant response to 5-HT with pA2 values of 6.8 (6.7-7.1, n = 12) and 7.1 (6.9-7.5, n = 12) respectively. The vagus nerve was depolarized by IBMX (100 microM) or forskolin (10 microM), the effects being similar to the maximum response to 5-HT. In the presence of IBMX (100 microM) or forskolin (10 microM) the ondansetron-resistant component of the response to 5-HT was enhanced and the 5-HT3 receptor-mediated component reduced. These results with DAU 6285 and SDZ 205-557 are consistent with a 5-HT4 receptor-mediated mechanism of the ondansetron-resistant depolarizing response to 5-HT.
D010129:4-Aminobenzoic Acid / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D017294:Ondansetron / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology*; D062366:para-Aminobenzoates
D001562:Benzimidazoles; D019086:Bridged Bicyclo Compounds, Heterocyclic; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D062366:para-Aminobenzoates; C074390:DAU 6285; C072790:2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester; D012701:Serotonin; D017294:Ondansetron; D010129:4-Aminobenzoic Acid