Stimulus Deprivation Increases Pineal Gsα and Gβ

Abstract: Denervation and other forms of stimulus deprivation cause an increase in the magnitude of subsequent responses, a phenomenon commonly referred to as denervation supersensitivity. This has been well demonstrated with the cyclic AMP response to norepinephrine in the pineal gland. In the present report, we address the question of whether stimulus deprivation alters α and β subunits of the GTP binding regulatory protein that stimulates adenylyl cyclase activity (Gs). Stimulus deprivation of the pineal gland was produced by denervation (superior cervical ganglionectomy), decentralization of the superior cervical ganglia, or by exposure of the animal to continuous lighting. All increased both the α and β subunits of Gs (Gsα and Gβ) by up to fourfold, as estimated using semiquantitative western blot technology. These effects were detectable after 1 day of stimulus deprivation and were sustained for 2 weeks. The stimulatory effects of constant light‐induced stimulus deprivation were also apparent by measuring cholera toxin‐dependent ADP‐ribosylation of Gsα, which revealed a fourfold increase in the amount of labeled substrate. The results of in vivo studies were confirmed with in vitro studies, which demonstrated a spontaneous increase in both Gsα and Gβ during 72 h of organ culture. The constant light‐induced increases in both Gsα and Gβ were prevented by continuous administration of isoproterenol (0.3 mg/kg/day), supporting the suggestion that adrenergic stimulation controls the levels of Gsα and Gβ. These studies indicate that stimulus deprivation increases both Gsα and Gβ. It appears that such increases play a central role in generating supersensitivity in the pineal gland and may play a role in supersensitivity in other systems.