Gastrin-releasing peptide is a transmitter mediating porcine gallbladder contraction.
We studied the role of gastrin-releasing peptide (GRP) for porcine gallbladder motility. Immunohistochemistry visualized nerve fibers containing GRP-like immunoreactivity in muscularis. GRP concentration dependently stimulated contractions of muscularis strips (ED50, 2.9 nM). Neuromedin B was less potent (ED50, 0.1 microM), suggesting existence of GRP-preferring receptors. GRP-induced contractions were unaffected by muscarinic antagonism (1 microM atropine), axonal blockade (1 microM tetrodotoxin), cholecystokinin (CCK) receptor antagonism (10 microM MK-329), or substance P desensitization (1 microM), supporting the existence of myogenic GRP receptors. The bombesin (BN) analogue D-Phe6-BN-(6-13)propylamide (PA) stimulated contractions (ED50, 3.3 nM) with low efficacy (29% of that of GRP). D-Phe6-BN-(6-13)PA (1 microM) shifted GRP concentration-response curves one log to the right. D-Phe6-BN-(6-13)PA interacted specifically with GRP receptors; while abolishing responses to GRP (1 nM), responses to substance P (0.1 microM) and CCK-8 (1 nM) were unchanged. Electrical stimulation (10 Hz, 0.5 ms, 10 V) caused a rapid onset-slow offset, tetrodotoxin-sensitive excitation. Atropine reduced the amplitude to 58% and caused a delayed, slow onset-slow decline response. D-Phe6-BN-(6-13)PA reduced the amplitude to 59% and caused a very rapid onset-rapid decline response. Atropine plus D-Phe6-BN-(6-13)PA abolished responses to nerve stimulation. Nerve stimulation caused significant release of GRP-like immunoreactivity. Thus two neural inputs were defined: a cholinergic rapid onset-rapid offset excitation and a delayed, slow onset-slow offset excitation caused by release and subsequent binding of GRP to GRP-preferring receptors.
Schjoldager
B
B
Department of Medical Physiology C, Panum Institute, University of Copenhagen, Denmark.
Poulsen
S S
SS
Schmidt
P
P
Coy
D H
DH
Holst
J J
JJ
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004558:Electric Stimulation; D005704:Gallbladder / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D019886:Gastrin-Releasing Peptide; D005768:Gastrointestinal Hormones / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D009412:Nerve Fibers / Q000502:physiology; D015287:Neurokinin B / Q000031:analogs & derivatives / Q000494:pharmacology; D010455:Peptides / Q000032:analysis / Q000494:pharmacology* / Q000502:physiology; D012844:Sincalide / Q000494:pharmacology; D013373:Substance P / Q000032:analysis / Q000494:pharmacology / Q000502:physiology; D013552:Swine; D013779:Tetrodotoxin / Q000494:pharmacology
D005768:Gastrointestinal Hormones; D010455:Peptides; D013373:Substance P; D013779:Tetrodotoxin; D001285:Atropine; D019886:Gastrin-Releasing Peptide; D015287:Neurokinin B; C038393:neuromedin B; D002217:Carbachol; D012844:Sincalide