Regulation of canine gallbladder motility by brain peptides.
BACKGROUND
Brain peptides alter most gastrointestinal functions, but their effects on gallbladder motility have not been examined in detail.


METHODS
Studies were conducted in awake, male beagle dogs.


RESULTS
Of 30 brain peptides evaluated, thyrotropin-releasing hormone (TRH) and calcitonin gene-related peptide (CGRP) inhibited CCK- and meal-induced gallbladder contraction. These responses were abolished by ganglionic blockade. Truncal vagotomy prevented the central inhibitory action of TRH but not that of CGRP, whereas noradrenergic blockade prevented the central inhibitory action of CGRP but not that of TRH. Muscarinic blockade did not prevent the relaxing effect of cerebral TRH but pretreatment with the vasoactive intestinal peptide (VIP) antagonist, (4Cl-D-Phe6-Leu17)VIP, significantly attenuated gallbladder relaxation induced by cerebral TRH: the combination of both VIP and muscarinic antagonists abolished TRH-induced gallbladder relaxation. alpha-Adrenergic receptor blockade but neither beta-adrenergic blockade nor adrenalectomy abolished gallbladder relaxation induced by cerebral CGRP. Intravenous infusion of VIP and norepinephrine inhibited CCK-induced gallbladder contraction and these responses were abolished dose dependently by intravenous infusion of (4Cl-D-Phe6-Leu17)VIP and phentolamine, respectively.


CONCLUSIONS
Cerebral TRH inhibits canine gallbladder contraction by stimulation of vagal outflow and subsequent release of VIP acting via its specific receptor whereas cerebral CGRP inhibits gallbladder contraction by stimulation of sympathetic, noradrenergic outflow via alpha-adrenergic receptors.
Lenz
H J
HJ
Department of Medicine, University of Hamburg, Germany.
Zimmerman
F G
FG
Messmer
B
B
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004435:Eating; D005704:Gallbladder / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects*; D009479:Neuropeptides / Q000494:pharmacology*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D009479:Neuropeptides; D014660:Vasoactive Intestinal Peptide; D013973:Thyrotropin-Releasing Hormone; D002766:Cholecystokinin; D003346:Corticotropin-Releasing Hormone; D015740:Calcitonin Gene-Related Peptide