Pharmacological characterization of 5-hydroxytryptamine-induced depolarization of the rat isolated vagus nerve.
A study has been made of the pharmacology of the 5-hydroxytryptamine (5-HT)-induced depolarization responses that can be recorded extracellularly from the rat isolated cervical vagus nerve. Phenylbiguanide (PBG) and 2-methyl-5-hydroxytryptamine (2-methyl-5-HT) were found to mimic the effects of 5-HT on the vagus nerve. Their EC50 values were respectively 2.0 fold and 3.9 fold greater than that of 5-HT. Metoclopramide behaved as a reversible competitive antagonist of depolarization induced by PBG and 2-methyl-5-HT, with pKB values of 6.48 +/- 0.04, respectively. These agreed well with the pKB value of 6.60 +/- 0.04 obtained previously for metoclopramide against 5-HT on the rat vagus nerve. 5-HT, PBG and 2-methyl-5-HT had no demonstrable agonist effects at non-5-HT receptors on the rat vagus nerve. Tropacaine and m-chlorophenylpiperazine were found to behave as reversible competitive antagonists of 5-HT-induced depolarization of the vagus nerve. The pKB values were 6.29 +/- 0.03 and 6.90 +/- 0.03, respectively. Quipazine, MDL 72222 and ICS 205-930 were also shown to be effective antagonists of 5-HT on the vagus nerve. However, although these compounds were highly potent, they all caused a marked concentration-dependent reduction in the amplitude of the maximum response to 5-HT. This behaviour was not consistent with a simple reversible competitive mechanism. The results are discussed with reference to the current classification of mammalian peripheral neuronal 5-HT receptors.
D000818:Animals; D001645:Biguanides / Q000378:metabolism; D003042:Cocaine / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011814:Quipazine / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D012702:Serotonin Antagonists; D014630:Vagus Nerve / Q000187:drug effects*
D001645:Biguanides; D010879:Piperazines; D012702:Serotonin Antagonists; C005862:tropacocaine; D012701:Serotonin; D011814:Quipazine; C045918:2-methyl-5-HT; D003042:Cocaine; C015068:1-(3-chlorophenyl)piperazine; C008846:phenyl biguanide