Central CCK‐8s receptors trigger the sigma ligand‐ and 5‐HT_1A agonists‐induced acceleration of post‐prandial colonic transit in rats

Abstract

The effects ofigmesine (JO 1784) and 5‐HT1A agonists (8‐OH‐DPAT, buspirone) on post‐prandial colonic transit were evaluated in conscious rats chronically fitted with an intracolonic catheter inserted into the proximal colon. Colonic transit time was evaluated by intracolonic administration of a radiolabelled marker ([51Cr]sodium chromate) and collection of the faeces, per hour, on a conveyor belt. In control studies, the colonic mean retention time was 7.8 ± 1.9 h and faecal dry matter was 50.1 ± 8.4%. Intraperitoneal treatment with igmesine (1 mg kg‐1) reduced the colonic mean retention time by 61.1 %, but was inactive at 0.1 and 0.25 mg kg‐1. Buspirone (10 mg kg‐1 IP) and 8‐OH‐DPAT (0.1 mg kg‐1) injected i.p. reduced the mean retention time. The stimulatory effect of buspirone on colonic transit was dose‐related (0.1–10 mg kg‐1). Neither igmesine, buspirone nor 8‐OH‐DPAT affected the faecal dry matter. Intracerebroventricular (i.c.v.) injection of igmesine (0.025 and 0.1 mg kg‐1) also reduced the post‐prandial mean retention time by 41.6 and 41.7%, respectively, without any effect on faecal dry matter. In contrast, intracerebroventricular injection of 8‐OH‐DPAT or buspirone had no effect on colonic mean retention time. Subcutaneous injection with BMY 14802 (1 mg kg‐1) completely prevented the igmesine‐ (0.1 mg kg‐1 i.c.v.) induced reduction of mean retention time; furthermore, spiroxatrine (0.5 mg kg‐1 s.c.) blocked both buspirone‐ (10mgkg‐1 i.p.) and 8‐OH‐DPAT‐ (0.1 mg kg‐1i.p.) induced stimulation of postpandial colonic transit. Intracerebroventricular but not i.p. injection of devazepide (10 μg kg‐1) inhibited the stimulating effect of igmesine, 8‐OH‐DPAT or buspirone on colonic transit, while L365,260 was inactive. In rats igmesine and 5‐HT1A agonists stimulate colonic transit by a mechanism involving the central release of CCK‐8s and/or the activation of supraspinal CCKergic pathways and these effects are mediated through CCKA‐type receptors.