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Major histocompatibility complex modulation of beta-adrenoceptor function.

Reciprocal interaction between beta-adrenoceptor specific ligand occupancy and alloantibody binding to specific antigens of cardiac and smooth muscle tissues was observed. Interference of alloimmune antibody fixation to both cardiac and oviductal tract preparations by beta 1 or beta 2 selective blockers, respectively, was obtained by means of indirect immunofluorescence assays. Reciprocally, alloimmune IgG and monoclonal antibodies directed to class I H-2 antigens, behaving as beta-adrenoceptor agonists, modified the contractility of both tissues, increasing intracellular levels of cyclic AMP (cAMP). Additionally, alloantibodies were also capable of inhibiting specific beta-adrenoceptor radioligand binding to purified cardiac and smooth muscle membranes. These data suggested a modulation of beta-adrenoceptor function by antibodies directed against H-2 class I histocompatibility molecules, probably through molecular interactions between both structures.

Animals↗

The role of beta- and alpha-adrenoceptors in the regulation of the stages of the sleep-waking cycle in the cat.

The effects of beta-adrenergic drugs alone and in combination with alpha-adrenergic drugs on the stages of the sleep-waking cycle were studied in adult cats. Polygraphic sleep recordings of 16 h showed that prenalterol (20 and 40 mg/kg i.p.), a beta 1-adrenoceptor-stimulating drug increased paradoxical sleep (PS) in a dose-related manner during 4-12 h. Salbutamol (40 mg/kg), a beta 2-adrenoceptor-stimulating drug, decreased PS during the first 4 h. Metoprolol (10 and 50 mg/kg), a relatively selective beta 1-adrenoceptor blocking drug, increased drowsy waking during the first 4 h. The larger dose also tended to decrease PS. Already at the lower dose metoprolol partially antagonized the PS increase produced by prazosin, an alpha 1-adrenoceptor blocking drug. Propranolol (5 mg/kg), a beta 1- and beta 2-adrenoceptor blocking drug, which alone decreases PS, antagonized the PS increase induced by phentolamine, an alpha 1- and alpha 2-adrenoceptor blocking drug. Atenolol (5 mg/kg), a poorly lipid-soluble beta-adrenoceptor blocking drug, failed to counteract phentolamine in increasing PS. Metoprolol (10 and 50 mg/kg) and propranolol (5 mg/kg) clearly potentiated the increase in drowsy waking and decrease in deep slow wave sleep and PS induced by clonidine (0.01 mg/kg), an alpha 2-adrenoceptor-stimulating drug. The results support the involvement of beta-adrenoceptors in the regulation of the sleep-waking cycle. A high level of beta-adrenergic activity may facilitate the production of PS. A low level of beta-adrenergic activity, especially in combination with a high level of alpha 2-adrenergic activity, may facilitate the production of drowsy waking. Central alpha 1- and beta 1-adrenoceptors may mediate opposite functions in the regulation of PS.

Albuterol↗

Beta 1 and beta 2 adrenergic receptors: their role in the regulation of paradoxical sleep in the rat.

The influences of beta adrenergic transmission on the regulation of paradoxical sleep (PS) were analysed in the rat. Pharmacological experiments have used beta 1,2 as well as preferential beta 1 or beta 2 compounds. The blockade of the beta 1 adrenoceptors induced a dose-related PS decrease, and stimulation of these preblocked receptors prevented this PS insomnia. SWS was generally not affected. It is concluded that beta 1 neurotransmission is directly involved in the regulation of PS.

Acebutolol↗

Cardiovascular effects of diazepam and chlordiazepoxide.

In open-chest dog preparations i.v. administration of diazepam and chlordiazepoxide caused increases in coronary blood flow and cardiac output while reducing blood pressure, heart rate, and myocardial contractile force. The decrease in force was independent of the alteration in coronary flow. Arterial--coronary sinus oxygen difference narrowed and myocardial oxygen consumption decreased. These data show that both diazepam and chlordiazepoxide exert an oxygen conserving action along with an increase in myocardial oxygen delivery and suggest that these drugs may be of benefit to the patient with coronary insufficiency by a direct effect on the cardiovascular system as well as through CNS-mediated antianxiety effects.

Animals↗

Delayed appearance of propranolol sensitivity in cultured heart cells.

Examination of the appearance of adrenaline responsiveness and propranolol sensitivity with culture age in myoblasts cultured from neonatal rat hearts shows that propranolol sensitivity lags behind adrenergic responsiveness. Such a finding may illustrate subtle differences in sites for agonist and antagonist at the beta-receptor of these cells.

Animals↗