Regulation by chronic drug administration of neuronal and cardiac calcium channel, beta-adrenoceptor and muscarinic receptor levels

Chronic administration of atropine (40-100 mg/kg, 23 days) produced a 29-33% increase in muscarinic receptors, measured by [³H]quinuclidinyl benzilate binding, in rat brain. Diisopropyl phosphorofluoridate (0.9 mg/kg, 14 days) produced a 35% decrease in muscarinic receptors. Propranolol administration (800 μg/kg/hr, 10 days) increased beta-adrenoceptors, measured by [³H]dihydroalprenolol binding, by 69 and 50% in brain and heart respectively. Isoproterenol administration (800 μg/kg/hr, 10 days) produced a 50% reduction in cardiac beta-adrenoceptors but did not alter brain receptors. These drug treatments were without effect on binding of the Ca²⁺ channel ligands, [³H]nimodipine and [³H]nitrendipine, to brain or heart respectively. However, chronic administration of nifedipine for 20 days (36 and 360 μg/kg/hr) did produce down-regulation of both cardiac and neuronal Ca²⁺ channels and a similar down-regulation of beta-adrenoceptors. Co-regulation of Ca²⁺ channels and neurotransmitter receptors may occur but may not be an automatic consequence of either receptor or channel regulation.