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Intracellular guanosine-5'-O-(2-thiodiphosphate) alters the dynamics of receptor-mediated responses in bullfrog sympathetic neurons

MA Simmons and RJ Mather

Department of Pharmacology, Marshall University, Huntington, West Virginia 25755-9310.

The mechanism by which intracellularly applied guanosine-5'-O-(2- thiodiphosphate) alters responses to chicken II luteinizing hormone- releasing hormone, muscarine, and substance P in bullfrog sympathetic neurons was examined. Whole-cell recordings were made from enzymatically dissociated single neurons. Guanosine-5'-O-(2- thiodiphosphate) was applied intracellularly by adding it to the pipette solution with fixed amounts of GTP. Guanosine-5'-O-(2- thiodiphosphate) did not affect the proportion of cells that responded to any of the agonists. Guanosine-5'-O-(2-thiodiphosphate) decreased the amplitude of the responses to submaximal concentrations of agonist. At maximal concentrations of agonist, guanosine-5'-O-(2- thiodiphosphate) did not decrease the response to the first application of agonist; however, with guanosine-5'-O-(2-thiodiphosphate) intracellularly, successive responses to maximal concentrations of agonist were decreased in amplitude and increased in time course. Intracellular guanosine-5'-O-(2-thiodiphosphate) did not accelerate the rate or magnitude of desensitization to substance P. A kinetic model of receptor-guanine nucleotide-binding protein (G protein) coupling predicts that a decrease in the available G protein pool should decrease both the magnitude and the time course of the build-up of active G proteins. The results are consistent with the hypothesis that guanosine-5'-O-(2-thiodiphosphate) binds tightly to G proteins, thereby effectively decreasing the available G protein pool with repeated agonist applications.

Volume 41, Issue 3, pp. 527-534, 03/01/1992
Copyright © 1992 by American Society for Pharmacology and Experimental Therapeutics




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