Involvement of CCK in the paraventricular nucleus of the hypothalamus in the CNS regulation of colonic motility

The effects of cholecystokinin octapeptide (CCK8), the CCK-A receptor antag onist, MK-329, and the CCK-B receptor antagonist, L-365, 260, microinfused into the paraventricular nucleus of hypothalamus (PVN) on colonic motor fun ction was investigated in awake rats, chronically implanted with a microinj ection cannula into the PVN and a catheter into the proximal colon. In fast ed rats, bilateral microinfusion of CCK8 at doses of 1.5 and 3.0 mu g/rat i nto the PVN stimulated colonic transit, as shown by a significant increase in the geometric center by 47 and 54%, respectively. This effect of CCK8 wa s site-specific to the PVN, since microinjection of the peptide into sites outside of but adjacent to PVN had no effect. In non-fasted rats, L-365,260 bilaterally microinjected into the PVN at a dose of 1.5 mu g/rat inhibited propulsive colonic motor function; colonic transit time significantly incr eased by 73% in comparison to the control condition. Microinfusion of the C CK-A antagonist into in the PVN did not affect colonic transit. These resul ts show that the PVN is a responsive site For the central CCK8-induced modu lation of colonic motility. The data suggest, that endogenous CCK in the pa raventricular nucleus of the hypothalamus unfolds a stimulatory effect on c olonic transit through action on CCK-B receptors, Copyright (C) 2000 S. Kar ger AG. Basel.