Calcitonin gene-related peptide evokes distinct types of excitatory response in guinea pig coeliac ganglion cells.

Pressure application of calcitonin gene-related peptide (CGRP) evoked in a population of guinea pig coeliac neurons 3 types of response: a fast, a slow and a biphasic depolarization. The responses were not appreciably affected in low Ca/high Mg or tetrodotoxin-containing Krebs solution. The fast depolarization was associated with a fall in membrane resistance; it was made larger on hyperpolarization and the estimated reversal potential was -24 mV. The fast response was reversibly blocked in a Na-free medium as well as by relatively high concentrations of d-tubocurarine (50-100 microM) but not by hexamethonium. The slow, CGRP-induced depolarization resistant to nicotinic and muscarinic antagonists, was associated with either a small increase or decrease of input resistance. Membrane hyperpolarization increased the slow response in the majority of coeliac neurons, with an estimated reversal potential of -44 mV. The biphasic depolarization displayed electrophysiological and pharmacological characteristics resembling the fast and slow responses. These results raise the possibility that CGRP acting via two distinct types of receptor elicits, respectively, a fast, Na-dependent excitatory response and a slow response, the mechanism of which remains to be established.