MUSCARINIC CHOLINERGIC RECEPTORS IN MOUSE PITUITARY-TUMOR CELLS - PROLONGED AGONIST PRETREATMENT DECREASES RECEPTOR CONTENT AND INCREASES FORSKOLIN-STIMULATED AND HORMONE-STIMULATED CYCLIC-AMP SYNTHESIS AND ADRENOCORTICOTROPIN SECRETION

  • 1 January 1985
    • journal article
    • research article
    • Vol. 232  (1) , 232-238
Abstract
Muscarinic receptor activation on the AtT-20 clonal line of mouse pituitary corticotrophs, inhibits forskolin-stimulated cAMP formation and ACTH secretion. In this study, the effect of prolonged receptor stimulation with the muscarinic agonist oxotremorine reduced, in a time-dependent manner, the ability of oxotremorine to inhibit the AtT-20 cell response to forskolin. Pretreatment with oxotremorine also reduced the density of muscarinic receptors without affecting the affinity of these sites for [3H]quinuclidinyl benzilate. In addition to densensitizing the muscarinic receptor, oxotremorine pretreatment also enhanced the ability of forskolin to stimulate cAMP formation and ACTH secretion. The apparent sensitizing effect on cAMP synthesis, extended to other muscarinic agents as well as other secretory agonists, was dependent on the oxotremorine concentration used during pretreatment and required at least 2 h of pretreatment. Enhancement of forskolin-stimulated cAMP accumulation by oxotremorine pretreatment was blocked by cycloheximide and reversed by the muscarinic antagonist, (-)-scopolamine, or by a 5 h recovery period after pretreatment. The data suggest that prolonged muscarinic receptor activation (rather than simple occupancy) leads to an enhancement of adenylate cyclase activity in AtT-20 cells; whether this effect is coupled to the progressive loss of the inhibitory function of the muscarinic receptor and the receptor down-regulation is unknown.