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Modulation by GTP of Basal and Agonist‐Stimulated Striatal Adenylate Cyclase Activity Following Chronic Blockade of D 1 and D 2 Dopamine Receptors: Involvement of G Proteins in the Development of Receptor Supersensitivity
Author(s) -
Schettini Gennaro,
Ventra Carmelo,
Florio Tullio,
Grimaldi Maurizio,
Meucci Olimpia,
Marino Adriano
Publication year - 1992
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1992.tb10997.x
Subject(s) - gtp' , medicine , endocrinology , receptor , dopamine receptor , adenylate kinase , cyclase , agonist , chemistry , sch 23390 , dopamine , g protein , biology , biochemistry , enzyme
Rats receiving injections of specific antagonists of dopamine receptors (SCH 23390 for D 1 , haloperidol for D 2 , and haloperidol + SCH 23390) once daily for 21 days develop a selective supersensitivity of the blocked receptors. To study the molecular correlates of these adaptive changes, we evaluated the involvement of GTP‐binding proteins in the development of supersensitivity of dopamine receptors. By means of adenylate cyclase studies, we tested whether any of the treatments modified the functional response to GTP in striata dissected from control and treated rats. Our data show that the chronic blockade of D 1 and/or D 2 receptors potentiates both basal and dopamine receptor‐stimulated adenylate cyclase activity in response to GTP. D1 receptor up‐regulation correlates with an increased adenylate cyclase response to GTP, whereas D 2 receptor up‐regulation is accompanied by an enhanced GTP‐induced inhibition of enzyme activity, in both basal and receptor‐activated conditions. This potentiation does not seem to match the changes in mRNA content of G s and G i ã subunits. Unexpectedly, however, a significant increase in G i ã subunit mRNA was found after the chronic blockade of D 1 receptors; this result could be explained by cross‐regulation between GTP‐binding protein‐mediated pathways. This cross‐regulation could serve as a protective mechanism whereby cells exposing up‐regulated receptors protect themselves from a condition of hyperactivity of the adenylate cyclase enzyme.