Mode of stimulation of gallbladder contraction by substance K.
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.
Yau
W M
WM
Department of Physiology, School of Medicine, Southern Illinois University, Carbondale 62901-6512.
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005704:Gallbladder / Q000187:drug effects / Q000502:physiology*; D006168:Guinea Pigs; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D015288:Neurokinin A / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D007546:Isoquinolines; D010879:Piperazines; D013779:Tetrodotoxin; D001285:Atropine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015288:Neurokinin A; D000109:Acetylcholine