Thyrotropin-releasing hormone interacts with vasoactive intestinal peptide-specific receptor in guinea pig cecal circular smooth muscle cells

Abstract

The relationship between thyrotropin-releasing hormone (TRH) binding sites and vasoactive intestinal peptide (VIP) receptors in circular muscle cells obtained from the guinea pig cecum was investigated using antagonists of VIP receptors and a selective receptor protection method. Both VIP10–28, a VIP antagonist, and atrial natriuretic peptide1–11 (ANP1–11), a VIP-specific receptor antagonist, completely inhibited 10 −5 M TRH-induced relaxation in a concentration-dependent manner. The muscle cells where cholecystokinin octapeptide (CCK-8) and TRH binding sites were protected completely preserved the inhibitory responses to TRH and ANP (a VIP-specific receptor agonist), and partially the inhibitory response to VIP. Peptide histidine isoleucine (PHI: a VIP-preferring receptor agonist) had no inhibitory effect on these cells. The muscle cells where CCK-8 and ANP (VIP-specific) receptors were protected completely preserved the inhibitory responses to TRH and ANP and partially the inhibitory response to VIP. PHI had no inhibitory effect on these cells. The muscle cells where CCK-8 and VIP receptors (both VIP-specific and VIP-preferring receptors) were protected preserved completely the inhibitory responses to TRH, VIP, ANP, and PHI. The muscle cells where CCK-8 and PHI (VIP-preferring) receptors were protected completely preserved the inhibitory response to PHI and partially the inhibitory response to VIP. TRH and ANP had no inhibitory effect on these cells. This study first demonstrates that TRH interacts with VIP-specific receptor in guinea pig cecal circular smooth muscle cells.