Inhibition of carbachol-stimulated phosphoinositide turnover by U-50,488H in rat hippocampus--involvement of GTP-binding protein.

Article date: 1991/6/19

PubMed ID: 1652445

Journal name: European journal of pharmacology (ISSN: 0014-2999)


The effect of U-50,488H, a selective kappa-opioid agonist, on carbachol-stimulated phosphoinositide (PI) turnover response in rat hippocampal slices was examined. U-50,488H which stimulates PI turnover response in this preparation (Periyasamy and Hoss, 1990, Life Sci. 47, 219), inhibited carbachol-stimulated PI turnover in a concentration-dependent manner with an IC50 value of 33 +/- 9.0 microM. The inhibitory effect of U-50,488H was not blocked by the kappa-selective antagonists, e.g., nor-binaltorphimine (10 microM), and MR2266 (10 microM), or tetrodotoxin (1 microM) suggesting that the effect of U-50,488H was mediated neither through the kappa-receptors nor through the release of an endogenous neurotransmitter(s). A Lineweaver-Burke plot of the stimulation of PI turnover by carbachol in the presence and absence of U-50,488H showed that the Km was not changed (11.4 +/- 3.4 and 11.5 +/- 2.6 microM) whereas the Vmax was reduced from 3849 +/- 460 to 1534 +/- 31 cpm indicating that the inhibition was non-competitive. U-50,488H also inhibited guanosine 5'-[beta, gamma-imido]triphosphate (Gpp[NH]p)-stimulated PI turnover in rat hippocampal membranes in a concentration-dependent manner with an IC50 value of 33 +/- 12 microM.(ABSTRACT TRUNCATED AT 250 WORDS)

Author List: Periyasamy S, Hoss W

Publication Types: Journal Article; Research Support, U.S. Gov't, P.H.S.

Substances mentioned in the article: Phosphatidylinositols; Pyrrolidines; Tritium; Ibotenic Acid; Serotonin; Tetrodotoxin; Quinuclidinyl Benzilate; 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Carbachol; Type C Phospholipases; GTP-Binding Proteins; Norepinephrine;

Mesh terms: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Carbachol/pharmacology; GTP-Binding Proteins/metabolism; Hippocampus/drug effects; Ibotenic Acid/pharmacology; In Vitro Techniques; Male; Norepinephrine/pharmacology; Phosphatidylinositols/metabolism; Pyrrolidines/pharmacology; Quinuclidinyl Benzilate/metabolism; Rats; Rats, Inbred Strains; Serotonin/pharmacology; Tetrodotoxin/pharmacology; Tritium; Type C Phospholipases/pharmacology;

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