Electrophysiological analysis of the actions of pituitary adenylyl cyclase activating peptide in the taenia of the guinea-pig caecum.

Abstract

The actions of pituitary adenylyl cyclase activating peptide (PACAP) on membrane potential and conductance were investigated in the taenia of the guinea-pig caecum. The possible role of PACAP in inhibitory transmission was also investigated. Membrane potentials of smooth muscle cells were measured by intracellular microelectrodes, in the presence of hyoscine and nifidepine (both 10(-6)M. To determine conductance changes, current was passed from external plate electrodes using the technique of Abe and Tomita (1968). PACAP-27 caused a concentration dependent hyperpolarization of the muscle with a maximum of 12-15 mV at 10(-6)M. The hyperpolarization caused by PACAP was associated with a substantial increase in membrane conductance. The hyperpolarization was abolished by apamin (10(-6)M), a blocker of small conductance, calcium-dependent, potassium channels, and was reduced to about 50% by suramin (10(-4)M), which is an antagonist of P2 receptors for purines. The hyperpolarization was not reduced by tetrodotoxin (2 x 10(-6)M), suggesting PACAP acts directly on the muscle. With continued exposure to PACAP, the hyperpolarization decayed back to resting membrane potential after several minutes, possibly due to receptor desensitization. Inhibitory junction potentials (IJPs) were markedly reduced in amplitude in the period of presumed receptor desensitization to PACAP, were abolished by tetrodotoxin, but were not affected by suramin. Apamin abolished the IJP and revealed a small excitatory junction potential. This study implies that PACAP released from nerve fibres in the taenia caeci hyperpolarizes the muscle via an opening of apamin-sensitive potassium channels. The action is probably through type I PACAP receptors.