Action of pituitary adenylate cyclase-activating polypeptide on ion transport in guinea pig distal colon

Abstract

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.

Pituitary adenylate cyclase activating polypeptide (PACAP) in the gastrointestinal tract of the rat: distribution and effects of capsaicin or denervation

“…There is evidence that this effect is mediated by apaminsensitive potassium channels (Schworer et al 1992). In addition, PACAP stimulates secretory processes, i.e., pepsinogen release from guinea-pig chief cells (Felley et al 1992) and ion transport in rat small intestine (Cox 1992) and in guinea-pig distal colon (Kuwahara et al 1993). In some of these studies, the effects of PACAP resemble those of VIP, suggesting activation of a common PA-CAP/VIP receptor.…”

“…Functional studies indicate that the effects of PACAP in the GI-tract are somewhat similar to those of VIP. PACAP stimulates pepsinogen release from gastric chief cells of the guinea-pig (Felley et al 1992) and stimulates ion transport in rat small intestine (Cox 1992) and in guinea pig distal colon (Kuwahara et al 1993). Additionally, PACAP induces relaxation of GIsmooth muscle in rat (Mungan et al 1992;Grider et al 1994), guinea pig (Schworer et al 1992;Katsoulis et al 1993;Jin et al 1994), and pig (Schwarzhoff et al 1995).…”

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

“…Intravenous injection of PACAP also enhances bicarbonate secretion in the duodenum (Takeuchi et al, 1997;Konturek et al, 2004). In the distal colon, PACAP acts through cholinergic and noncholinergic neurons to evoke chloride secretions (Kuwahara et al, 1993). In human colonic T84 cells, PACAP also regulates chloride secretion in a Ca 2ϩ -dependent manner .…”

Effects of cholera toxin on the potential difference and motor responses induced by distension in the rat proximal small intestine in vivo

“…In Ussing chambers, VIP evokes secretion both indirectly via activation of neurons and directly via an action on the mucosa (23). Furthermore, VIP has been reported to induce slow depolarizations in submucous neurons that were presumably VIP secretomotor neurons (27).…”