The effects of ethanol on beta-adrenergic receptor-adenylate cyclase (AC) systems were studied in cerebral cortex, pineal gland and heart. In cerebral cortex, ethanol, in vitro, stimulated AC activity by acting at the receptor and Ns. These effects were also reflected in ligand binding studies. Ethanol also affected agonist binding to heart beta-adrenergic receptors, and the results were consistent with a primary site of action at Ns. In pineal glands in culture, ethanol enhanced agonist-stimulated cyclic AMP and melatonin production. After chronic, in vivo, ethanol treatment, the function of each beta-adrenergic receptor system was altered. In cortex, decreased stimulation of AC activity by agonist and guanine nucleotides occurred, and ligand binding studies indicated an uncoupled receptor system, similar to changes seen during desensitization. In heart, the number of beta-adrenergic receptors was reduced, compatible with homologous desensitization, but agonist binding indicated a possible increased sensitivity to agonist. In rat pineal, decreased sensitivity of AC to agonist was observed, which eliminated the normal circadian rhythm. In contrast to the effects of ethanol on stimulatory receptor-AC systems, little effect was seen in several inhibitory receptor-AC systems. Ethanol also affected muscarinic receptor coupling to polyphosphoinositide breakdown. After chronic ingestion of ethanol by mice, there was increased sensitivity of this system to a muscarinic cholinergic agonist, which correlated with a previously-demonstrated increase in muscarinic cholinergic receptor number. This change may be associated with specific ethanol withdrawal symptoms. The studies illustrate that ethanol has specific sites of action in the CNS and periphery, and that adaptation occurs at these sites in animals that develop tolerance and physical dependence.
