AJP - Gastrointestinal and Liver Physiology, Vol 259, Issue 5 838-G841, Copyright © 1990 by American Physiological Society
Mode of stimulation of gallbladder contraction by substance K
W. M. Yau
Department of Physiology, School of Medicine, Southern Illinois University, Carbondale 62901-6512.
Substance K (SK) contracted the guinea pig gallbladder in vitro by
predominantly acting on the neurokinin (NK2) receptors localized on the
smooth muscle. A comparison of the 50% effective dose among the tachykinins
showed that SK is 20 and 176 times more active than neurokinin B (NKB) and
substance P (SP), respectively. Senktide, a synthetic NKB agonist with
presumably a specificity for only NK3 receptor subtype, was completely
inactive even when tested at 6 x 10(-6) M. Studies on both atropine-treated
tissues and [3H]acetylcholine release from myenteric plexus have revealed a
minor action of SK by way of a stimulation on the intramural cholinergic
neurons. There was still a residual 77.4% SK-evoked contraction that was
not blocked by atropine. However, the SK-induced contraction was completely
abolished in the presence of
1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine, a direct protein kinase C
(PKC) inhibitor. This latter observation suggests a link in the
PKC-specific pathway of intracellular signal transduction initiated by NK2
receptor activation on the gallbladder musculature. The preponderance of
NK2 receptor subtype further implies a unique functional role it may play
in gallbladder contractility.
