Evidence that G(z)-proteins couple to hypothalamic 5-HT(1A) receptors in vivo.

摘要: Using in situ hybridization and immunoblot analysis, the present studies identified Gz mRNA Gz-protein hypothalamic paraventricular nucleus. The role of Gz-proteins 5-HT1Areceptor signaling was examined vivo . Activation 5-HT1A receptors increases secretion oxytocin ACTH, but not prolactin. Intracerebroventricular infusion (3–4 d) antisense oligodeoxynucleotides, with different sequences phosphorothioate modification patterns, reduced levels nucleus, whereas missense oligodeoxynucleotides had no effect. Neither nor oligodeoxynucleotide treatment altered basal plasma oxytocin, or prolactin, when compared untreated controls. An antisense-induced decrease paralleled by a significant ACTH responses to agonist 8-hydroxy-dipropylamino-tetralin (8-OH-DPAT). In contrast, prolactin response 8-OH-DPAT (which cannot be blocked antagonists) inhibited oligodeoxynucleotides. are only members Gi/Go-protein family that inactivated pertussis toxin. control experiment, toxin (1μg/5 μl, i.c.v.; 48 hr before challenge) did inhibit response, potentiated eliminated 8-OH-DPAT. Thus, toxin-sensitive Gi/Go-proteins do mediate receptor-mediated increase secretion. Combined, these provide first evidence for key coupling 5-HT1Areceptors effector mechanisms.