Hippocampal and Cerebellar β‐Adrenergic Receptors and Adenylate Cyclase Are Differentially Altered by Chronic Ethanol Ingestion

Abstract

Chronic ethanol ingestion by mice resulted in the loss of high-affinity beta-adrenergic agonist binding sites and a significant decrease in activation of adenylate cyclase by guanine nucleotides and beta-adrenergic agonists in the hippocampus, although no significant change was noted in the total number of beta-adrenergic receptors, as defined by the binding of the antagonist [125]iodocyanopindolol. In cerebellum, chronic ethanol ingestion resulted in a 16% decrease in the total concentration of beta-adrenergic receptors and in a decrease in the affinity for agonist of the high-affinity beta-adrenergic agonist binding sites. However, neither the amount of the high-affinity agonist binding sites nor the activation of adenylate cyclase by agonist was affected. The different responses to ethanol in hippocampus and cerebellum may result from quantitative differences in distribution of beta 1- and beta 2-adrenergic receptors in the tested brain areas and/or differential effects of ethanol on stimulatory guanine nucleotide binding protein in these brain areas.

Phosphodiesterase regulation of alcohol drinking in rodents

“…Chronic alcohol consumption reduced stimulus-dependent AC activity in the cortex (Saito, Lee, Hoffman, & Tabakoff, 1987) and hippocampus (Valverius, Hoffman, & Tabakoff, 1989), but inconsistently in cerebellar neurons (Valverius et al, 1989; Wand, Diehl, Levine, Wolfgang, & Samy, 1993) of mice. In rats, increased expression of mRNA for the PKA inhibitor PKI in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), and amygdala was demonstrated after chronic intermittent alcohol vapor exposure in rats (Repunte-Canonigo, Lutjens, van der Stap, & Sanna, 2007), while reduced levels of phosphorylated CREB were observed in the cortex, CeA, and medial amygdala (MeA) during withdrawal from chronic consumption of an alcohol-containing liquid diet (Pandey, Roy, & Mittal, 2001; Pandey, Roy, & Zhang, 2003).…”

G-protein regulation of adenylate cyclase activity in rat prostatic membranes after chronic ethanol ingestion

“…We tested whether the observed increase of basal adenylate cyclase was accompanied by a decrease of GTPase activity in prostatic membranes from ethanol-fed rats. Basal GTPase activity was not modified by chronic ethanol ingestion in rat prostatic membranes (655 ± 33 and 616 ± 55 pmol 32 Pi released/min/mg protein for control and ethanol-treated rats, respectively). Figure 7A shows the saturation of this enzyme by increasing concentrations of GTP.…”

“…In fact, when we studied the behavior of another receptor-mediated event in the present experimental model, we observed that ␤-adrenoceptor stimulation of adenylate cyclase activity increased in prostate after chronic ethanol intake. Similar protocols of ethanol feeding also resulted in disparities among tissues, for example, an increase in ␤-agonist-stimulated adenylate cyclase activity in rat myocardium [31] or in the cerebellar tissues, but not in hippocampus from ethanol-fed mice [32].…”

“…The tubes were kept on an ice bath for 10 min and centrifuged thereafter at 2,000g for 12 min at 4°C. An aliquot of 0.5 ml of supernatant was counted to determine the release of 32 Pi. High-affinity GTPase activity was determined after subtracting the amount of 32 Pi released in the presence of 500 M GTP from the total amount of 32 Pi released.…”

Effects of Toluene Exposure on Signal Transduction: Toluene Reduced the Signaling via Stimulation of Human Muscarinic Acetylcholine Receptor m2 Subtypes in CHO Cells

“…Alcohol inhibits the function of 5-hydoxytryptamine (serotonin) receptors (10,11). The in vivo effects of ethanol on the characteristics of the binding of agonists to b-adrenergic receptors and the activity of adenylyl cyclase in the rat brain were reported (12).…”