Involvement of CCK in the paraventricular nucleus of the hypothalamus in the CNS regulation of colonic motility.
The effects of cholecystokinin octapeptide (CCK(8)), the CCK-A receptor antagonist, MK-329, and the CCK-B receptor antagonist, L-365, 260, microinfused into the paraventricular nucleus of hypothalamus (PVN) on colonic motor function was investigated in awake rats, chronically implanted with a microinjection cannula into the PVN and a catheter into the proximal colon. In fasted rats, bilateral microinfusion of CCK(8) at doses of 1.5 and 3.0 microg/rat into the PVN stimulated colonic transit, as shown by a significant increase in the geometric center by 47 and 54%, respectively. This effect of CCK(8) was 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 microg/rat inhibited propulsive colonic motor function; colonic transit time significantly increased by 73% in comparison to the control condition. Microinfusion of the CCK-A antagonist into in the PVN did not affect colonic transit. These results show that the PVN is a responsive site for the central CCK(8)-induced modulation of colonic motility. The data suggest, that endogenous CCK in the paraventricular nucleus of the hypothalamus unfolds a stimulatory effect on colonic transit through action on CCK-B receptors.
Mönnikes
H
H
Department of Internal Medicine, Philipps University of Marburg, Germany. hubert.moennikes@charite.de
Tebbe
J
J
Grote
C
C
Sonntag
A
A
Pluntke
K
K
Sturm
K
K
Arnold
R
R
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology*; D003106:Colon / Q000294:innervation / Q000502:physiology*; D020109:Devazepide / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000502:physiology*; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010671:Phenylurea Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000502:physiology
D001570:Benzodiazepinones; D010446:Peptide Fragments; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C410885:cholecystokinin 8; C058121:L 365260; D002766:Cholecystokinin; D020109:Devazepide