Kuwahara A, Kuwahara Y, Mochizuki T, Yanaihara N
Department of Molecular Physiology, National Institute for Physiological Sciences, Okazaki, Japan.
Am J Physiol. 1993 Mar;264(3 Pt 1):G433-41. doi: 10.1152/ajpgi.1993.264.3.G433.
The aim of the present study was to investigate the action of pituitary adenylate cyclase-activating polypeptide (PACAP) on ion transport in the guinea pig distal colon. Submucosal/mucosal segments from distal colon were mounted in Ussing flux chambers, and increases in short-circuit current (Isc) were used as an index of secretion. Serosal addition of PACAP-38 and PACAP-27 produced concentration-dependent (10(-10)-10(-6) M) increases in Isc. Furosemide and chloride-free solutions significantly reduced the PACAP-evoked responses. Tetrodotoxin (TTX) completely blocked PACAP-evoked responses. Atropine significantly reduced the PACAP-evoked responses but did not abolish the responses. The results suggest that PACAP evokes chloride secretion through cholinergic and noncholinergic neural mechanism. Vasoactive intestinal polypeptide (VIP), peptide histidine-isoleucine amide, and helodermin evoked Isc in a concentration-dependent manner. Atropine reduced but did not abolish the VIP- and related peptides-evoked responses. TTX also significantly decreased the responses to higher concentrations of VIP and related peptides but did not abolish the responses. The results suggest that VIP and related peptides act on both submucosal neurons and the epithelial cell itself. VIP tachyphylaxis significantly decreased PACAP-38- and PACAP-27-evoked responses. These results provide evidence that PACAP recognizes, in some part, VIP receptors in the submucosal neurons to evoke chloride secretion.
本研究的目的是探讨垂体腺苷酸环化酶激活多肽（PACAP）对豚鼠远端结肠离子转运的作用。将远端结肠的黏膜下层/黏膜段安装在尤斯灌流小室中，短路电流（Isc）的增加用作分泌指标。向浆膜侧添加PACAP-38和PACAP-27可使Isc呈浓度依赖性（10⁻¹⁰ - 10⁻⁶ M）增加。呋塞米和无氯溶液显著降低了PACAP引起的反应。河豚毒素（TTX）完全阻断了PACAP引起的反应。阿托品显著降低了PACAP引起的反应，但并未消除该反应。结果表明，PACAP通过胆碱能和非胆碱能神经机制引起氯离子分泌。血管活性肠肽（VIP）、肽组氨酸异亮氨酸酰胺和海蜥蜴肽以浓度依赖性方式引起Isc增加。阿托品降低但并未消除VIP及相关肽引起的反应。TTX也显著降低了对较高浓度VIP及相关肽的反应，但并未消除该反应。结果表明，VIP及相关肽作用于黏膜下神经元和上皮细胞本身。VIP快速耐受显著降低了PACAP-38和PACAP-27引起的反应。这些结果提供证据表明，PACAP在一定程度上识别黏膜下神经元中的VIP受体以引起氯离子分泌。
