The action of vasoactive intestinal peptide antagonists on peptidergic modulation of the squid Schwann cell.

1. The effects of two specific antagonists of vasoactive intestinal peptide (VIP) receptors were investigated on the VIP-induced hyperpolarization of the membrane potential of the Schwann cell of the giant nerve fibre of the tropical squid. 2. Both (pCl-D-Phe6,Leu17)VIP and (N-Ac-Tyr1,D-Phe2)-GRF(1-29)amide competitively and reversibly blocked the effects of VIP in this preparation with the former compound being more potent than the latter. 3. The blocking actions of both antagonists were specific for the responses of this preparation to VIP. They did not block the actions of carbachol, DL-octopamine or substance P. 4. Both antagonists also reduced the effectiveness of an endogenous VIP-like component in the normal hyperpolarizing action of giant axon activity on the membrane potential of the Schwann cell, with the same potency ratio as for their actions on the effects induced by the exogenous application of VIP.