INTERACTION BETWEEN ATRIAL-NATRIURETIC-PEPTIDE AND VASOACTIVE-INTESTINAL-PEPTIDE IN GUINEA-PIG CECAL SMOOTH-MUSCLE

Backgrounds & Aims: The role of atrial natriuretic peptide (ANP) in gastrointestinal motility is still unclear. The aim of this study was to investigate the relationship between ANP and vasoactive intestinal peptide (VIP) in guinea pig cecal circular smooth muscle cells. Methods: The inhibition of I-125-ANP binding or I-125-VIP binding to cecal smooth muscle cells was assessed using unlabeled peptides (i,e., ANP, ANP fragments, VIP, secretin, and peptide histidine isoleucine); the effect of ANP, ANP fragments, and VIP on muscle contraction stimulated by 1 mu mol/L carbachol was assessed; and the inhibitory effects of ANP 1-11 on VIP-induced relaxation, ANP 1-11 and VIP 10-28 (a VIP antagonist) on ANP-induced relaxation, and nitric oxide production inhibitors on ANP-induced relaxation were assessed. Results: The specific binding of I-125-ANP was inhibited completely by unlabeled ANP and VIP in a dose-dependent manner but only slightly inhibited by secretin and peptide histidine isoleucine. ANP 1-11 and C-atrial natriuretic factor inhibited the binding of I-125-ANP With a lower affinity than ANP, ANP only partly inhibited I-125-VIP binding, ANP and VIP inhibited 1 mu mol/L carbachol-induced contraction in a dose-dependent manner. ANP 1-11 significantly inhibited VIP-induced relaxation. ANP 1-11, VIP 10-28, and NO production inhibitors completely inhibited ANP-induced relaxation. Conclusions: The results of the study showed that ANP 1-11 antagonized ANP-induced relaxation and that ANP stimulated NO production and subsequently induced relaxation via a receptor to which VIP binds.