Background-The effect of commonly ingested alcoholic beverages on gastric acid output and release of gastrin in humans is unknown. Aim and Methods-In 16 healthy humans the effect of some commonly ingested alcoholic beverages produced by fermentation plus distillation (for example, whisky, cognac, calvados, armagnac, and rum) or by alcoholic fermentation (beer,

Only during the last 15 years have systematic and controlled studies on the action of pure ethanol and some commonly ingested alcoholic beverages on gastric acid secretion and release of gastrin in humans been published (1)(2)(3)(4)(5)(6)(7)(8). Pure ethanol in low concentrations (≤4% vol/vol) is a mild stimulant of gastric acid output, whereas at higher concentrations, it has either no effect or a mildly inhibitory one (5). Alcoholic beverages with low ethanol content (beer and wine) are powerful stimulants of gastric acid output and gastrin release; the effect of beer is equal to the maximal acid output (5-8). Beverages with a higher ethanol content (e.g., whisky, gin, cognac) do not stimulate gastric acid output or release of gastrin (5, 7).The ethanol content in beer (4% vol/vol) and wine (10% vol/vol) can be only partially or not at all responsible for the marked gastric acid secretory responses to beer and wine. Thus, nonalcoholic ingredients in beer or wine are most likely responsible for the stimulatory gastric action of these alcoholic beverages. The intensive search for the stimulatory substances in beer has proved that none of the known nonalcoholic stimulants of gastric acid output present in beer either alone or in combination can be implicated (6).In a recent study (7), we reported that alcoholic beverages produced by fermentation (such as beer, wine, champagne, and sherry), but not by distillation (such as whisky, cognac, calvados, armagnac, Bacardi, Pernod, Cointreau, and Campari), are powerful stimulants of gastric acid output and release of gastrin. In addition, we found that the alcoholic beverage constituents that stimulate gastric acid output and release of gastrin are produced during the process of fermentation and removed during the following process of distillation (7).We used yeast-fermented glucose as a simpler model of beer in order to look for the powerful stimulants of gastric acid output produced during the process of alcoholic fermentation (6, 9). Alcoholic fermentation is the catabolism of glucose to pyruvate (e.g., glycolysis) and of pyruvate to ethanol by yeast. Yeast-fermented glucose (11.5% wt/vol) has been shown to mimic the effects of beer on gastric acid output and release of gastrin (6, 9). Whereas beer has a great number of unknown substances, yeastfermented glucose is a relatively pure solution.The aim of the present investigation was to separate and identify the substances in fermented glucose and alcoholic beverages that are responsible for their powerful stimulatory action on gastric acid output and release of gastrin in nonalcoholic healthy humans. Methods SubjectsThirty-five healthy young male (n = 20) and female (n = 15) volunteers (age, 21-37 years; body weight, 50-87 kg) were studied. All subjects were in good health and had a normal physical examination, electrocardiogram, and laboratory tests, including blood count, platelets, prothrombin time, aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, amylase, lipase, creatinine, electrolytes...

Chronic treatment of rats with R-PIA 'in vivo' desensitized adenosine A1 receptor-mediated inhibition of adenylyl cyclase in brain plasma membranes and increased basal and forskolin-stimulated adenylyl cyclase. The adenosine A1 receptor agonist CHA (cyclohexyl adenosine) inhibited forskolin-stimulated adenylyl cyclase in synaptic plasma membranes from control rats but failed to do so in membranes isolated from rats treated with R-PIA. This loss of response was accompanied with a significant decrease in both, total number of adenosine A1 receptors and steady-state level of alpha-Gi in synaptic plasma membranes. An increase in the steady-state level of alpha-Gs in synaptic plasma membranes was also observed by R-PIA treatment. Concurrently, a significant increase of adenosine A1 receptors was observed in microsomes and coated vesicles. These results demonstrate adenosine A1 receptor desensitization in rat brain by 'in vivo' treatment with R-PIA and suggest a role for coated vesicles in the internalization of G-protein coupled receptors.

Clathrin-coated vesicles purified from bovine brain express adenosine A1 receptor binding activity. N6-Cyclohexyl[3H]adenosine [( 3H]CHA), an agonist for the A1 receptor, binds specifically to coated vesicles. High and low agonist affinity states of the receptor for the radioligand [3H]CHA with KD values of 0.18 and 4.4 nM, respectively, were detected. The high purity of coated vesicles was established by assays for biochemical markers and by electron microscopy. Binding competition experiments using agonists (N6CHA, N-cyclopentyladenosine, 5'-(N-ethylcarboxamido)adenosine, and N6-[(R)- and N6-[(S)-phenylisopropyl]adenosine) and antagonists (theophylline, 3-isobutyl-1-methylxanthine, and caffeine) confirmed the typical adenosine A1 nature of the binding site. This binding site presents stereospecificity for N6-phenylisopropyladenosine, showing 33 times more affinity for N6-[(R)- than for N6-[(S)-phenylisopropyl]adenosine. The specific binding of [3H]CHA in coated vesicles is regulated by guanine nucleotides. [3H]CHA specific binding was decreased by 70% in the presence of the hydrolysis-resistant GTP analogue guanyl-5-yl-imidodiphosphate. Bovine brain coated vesicles present adenylate cyclase activity. This activity was modulated by forskolin and CHA. The results of this study support the evidence that adenosine A1 receptors present in coated vesicles are coupled to adenylate cyclase activity through a Gi protein.