Opiate and dopamine stimulate different GTPase in striatum: Evidence for distinct modulatory mechanisms of adenylate cyclase

F. Tirone, M. Parenti, A. Groppetti

Research output: Contribution to journalArticlepeer-review

Abstract

Previous studies demonstrated that opiate inhibition of adenylate cyclase (AC) in striatal membranes is related to an opiate-stimulated GTPase with a low Km. Dopamine (DA) also dose-dependently activates a high affinity GTPase, with a pattern of stimulation and a receptor selectivity (D1 type) similar to those observed in DA activation of striatal AC. Moreover, the DA- and the opiate-sensitive GTPase activities have different sensitivities to agents that affect the inhibition of AC, such as Na+ and N-ethylmaleimide (NEM), or the stimulation, such as cholera toxin (CTX). Thus, the impairment of opiate-dependent inhibition of AC in the absence of Na+ ions or after NEM pretreatment of the membranes is parallel with preferential impairment of the opiate-dependent GTPase. On the contrary, selective blocking by CTX of the DA-dependent GTPase leads to the enhancement of AC stimulation by DA. These results suggest that DA activation of striatal AC is related to a GTPase that is specifically stimulated by DA and is associated with the Ns protein. A distinct Ni protein seems to be responsible for the opiate effect on AC and GTPase.

Original languageEnglish
Pages (from-to)327-329
Number of pages3
JournalJournal of Cyclic Nucleotide and Protein Phosphorylation Research
Volume10
Issue number4
Publication statusPublished - 1985

ASJC Scopus subject areas

  • Biochemistry

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