Pharmacological characterization of 5‐hydroxytryptamine‐induced depolarization of the rat isolated vagus nerve

Abstract

1 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. 2 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. 3 Metoclopramide behaved as a reversible competitive antagonist of depolarization induced by PBG and 2-methyl-5-HT, with pK_B values of 6.48 ± 0.04 and 6.64 ± 0.04, respectively. These agreed well with the pK_B 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. 4 Tropacaine and m-chlorophenylpiperazine were found to behave as reversible competitive antagonists of 5-HT-induced depolarization of the vagus nerve. The pK_B values were 6.29 ± 0.03 and 6.90 ± 0.03, respectively. 5 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. 6 The results are discussed with reference to the current classification of mammalian peripheral neuronal 5-HT receptors.