Relationships between gastric motility and gastric vagal afferent responses to CCK and GRP in rats differ.
The brain-gut peptides cholecystokinin (CCK) and the mammalian bombesin-like peptide gastrin-releasing peptide (GRP) suppress food intake. Vagotomy blocks CCK- but not bombesin (BN)-induced feeding suppression, demonstrating differential vagal contributions. We examined the relationship between the ability of CCK and the active fragment of GRP, GRP-(18-27), to stimulate gastric vagal afferent activity and their ability to elicit changes in gastric motility. We also examined ligated cervical vagal segments and revealed specific 125I-CCK vagal binding without evidence of radiolabeled BN binding sites. Both close arterial and intraperitoneal CCK and GRP-(18-27) produced dose-dependent increases in activity in gastric vagal mechanoreceptive afferents. CCK dose dependently decreased gastric pressure without altering antral wall tension, whereas GRP-(18-27) dose dependently increased both gastric pressure and peak antral wall muscle tension. These results suggest that GRP-(18-27) activates gastric vagal afferents secondary to its stimulation of gastric motor effects. CCK activates this same population of vagal afferents independent of changes in gastric tension, suggesting a direct action of CCK at functional vagal CCK receptors.
Schwartz
G J
GJ
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
Moran
T H
TH
White
W O
WO
Ladenheim
E E
EE
D000818:Animals; D001839:Bombesin / Q000494:pharmacology*; D002766:Cholecystokinin / Q000494:pharmacology*; D005769:Gastrointestinal Motility; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000378:metabolism; D013270:Stomach / Q000294:innervation*; D014630:Vagus Nerve / Q000166:cytology / Q000187:drug effects*
D010446:Peptide Fragments; D011949:Receptors, Cholecystokinin; C040794:neuromedin C; D002766:Cholecystokinin; D001839:Bombesin