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Gastrin-releasing peptide is a transmitter mediating porcine gallbladder contraction

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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.
OriginalsprogEngelsk
TidsskriftAmerican Journal of Physiology (Consolidated)
Vol/bind260
Udgave nummer4 Pt 1
Sider (fra-til)G577-85
ISSN0002-9513
StatusUdgivet - apr. 1991

ID: 296952