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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 125 I-ANP binding or 125 I-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 μmol/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 125 I-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 125 I-ANP with a lower affinity than ANP. ANP only partly inhibited 125 I-VIP binding. ANP and VIP inhibited 1 μmol/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.

Background/Aims: The functional receptors for endothelin (ET) in colonic smooth muscle are still unknown. This study investigated the expression of ET receptors in isolated circular smooth muscle cells of guinea pig cecum. Methods: Inhibition of 125I-ET-1 binding was examined using unlabeled ET-1, ET-2, ET-3, sarafotoxin 6c (S6c), and ETA antagonists. Expression of the ET-receptor message was investigated using reverse-transcription polymerase chain reaction. The contractile potency of the ET family and the inhibitory effect of ETA antagonists on ET-1-induced contraction were also investigated. Results: Unlabeled ET-1, ET-2, and ET-3 inhibited the specific binding of 125I-ET-1 in a concentration-dependent manner, but the inhibitory effect of ET-3 was smaller than those of ET-1 and ET-2. At a 10−6 mol/L concentration of S6c, the specific binding of 125I-ET-1 was 24.7%. S6c had clearly reached maximal inhibition. Abundant polymerase chain reaction products for both the ETAand the ETB message were observed. ET-1 and ET-2 showed similar contractile potency, but ET-3-induced and S6c-induced contractions were significantly less potent than the ET-1-induced contraction. A significant response to S6c was obtained at a concentration as low as 10−10 mol/L. The ETA antagonists BQ-123 and FR 139317 significantly inhibited ET-1-induced contraction. Conclusions: The results show a direct contractile effect of ETs on circular smooth muscle of guinea pig cecum and the presence of both ETA- and ETB-receptor subtypes.