Effect on beta adrenergic receptors of tachyphylaxis on the sensitivity of smooth muscle in the bronchi to beta adrenergic receptor agonists in bronchial asthma

The study involved 30 subjects: 15 healthy individuals and 15 patients with atopic bronchial asthma of the moderate degree. Salbutamol was administered to asthmatic patients in the intravenous infusion for 7 days. beta-adrenergic receptor density in the lymphocytes and FEV1 were evaluated before and after therapy. Moreover, isoprenaline test was carried out to evaluate the sensitivity of the bronchial smooth muscle to beta-agonist. The test was performed prior to and after salbutamol therapy. It was found that beta-receptor agonist statistically significantly decreases beta-adrenergic receptor density. Equivalently, bronchial smooth muscle is less sensitive to beta-agonist in the same degree as a decrease in beta-adrenergic receptor density in the peripheral blood lymphocytes.     

Effect of a beta 2-blocker on the adrenergic receptors of lymphocytes in hypertension

A short-term effect of propranolol on beta 2-adrenoceptor density in mononuclear lymphocytes was studied in 15 male patients with essential hypertension. According to receptor density alterations the hypertensive subjects were divided into two groups. In the first group lymphocyte beta 2-receptor density increased substantially (3 times, on the average). Propranolol had a weak antihypertensive effect in this group, with the initially low plasma renin activity remaining unchanged after the treatment. The patients of the second group, on the contrary, revealed features of sympathetic hyperactivity and a decrease (2 times on the average) in lymphocyte beta 2-receptor density. Propranolol administration caused a decline in the initially normal or elevated plasma renin activity as well as in systolic arterial blood pressure and heart rate.     

Effect of the adrenergic beta receptor blocker propranolol on the dilatation of cerebrocortical vessels evoked by arterial hypoxia

In order to elucidate the importance of adrenergic beta receptors in the regulation of cerebral microcirculation during arterial hypoxia, chloralose anaesthetized cats were treated with propranolol hydrochloride. Arterial hypoxia, lasting for approximately 4 min, was induced by respiring the animals with a gas mixture containing 7% oxygen balanced in nitrogen gas. Arterial hypoxia was induced in the same animals before and during continuous infusion of propranolol (0.05 mg/kg/min into the lingual artery). Cerebrocortical vascular volume ( CVV ) and NADH fluorescence were measured through a cranial window with a microscope fluororeflectometer . Control arterial hypoxia (no treatment) increased CVV and NADH reduction by 22.2 +/- 2% and 20.4 +/- 2.1%, respectively. Following 1 mg/kg propranolol treatment arterial hypoxia of the same severity resulted in only approximately 2/3 of the CVV response obtained during the control arterial hypoxia. Since arterial hypoxia induced similar changes in arterial blood gases, arterial blood pressure, and intracranial pressure in both cases, our results indicate that the cortical vasodilatation occurring during arterial hypoxia is due, at least in part, to the activation of adrenergic beta receptors.     

Identification of beta adrenergic receptors in rat hypothalamus.

(-)-[3H]-Dihydroalprenolol((-)[3H]DHA) binding in the rat hypothalamus appears to possess all the characteristics expected of physiologically relevant beta-adrenergic receptors. Binding of (-)-[3H]DHA to the hypothalamic sites was rapid (k1 = 1.3 X 10(-7) min-1) and also rapidly reversible. Binding was saturable at low concentrations of ligand (approximately 50-100 nM). The dissociation constant (KD) of (-)-[3H]DHA binding determined by equilibrium analysis was 19 nM. Binding displayed beta-adrenergic specificity. beta-Adrenergic agonists inhibited binding in the following order of potency: (-)-isoproterenol congruent to (-)-epinephrine greater than (-)-norepinephrine. Specific beta-adrenergic antagonists (-)-propranol and (-)-alprenolol inhibited binding at low concentrations (KD = 25-50nM) whereas the alpha-antagonist phentolamine inhibited binding at very high concentration (KD = 42 micron). Interactions of both agonists and antagonists with the sites showed stereoselectivity. The (-)-isomers of all beta-adrenergic agents tested were more potent than their respective (+)-isomers. These results suggest that specific receptor sites for beta-adrenergic catecholamines are present in rat hypothalamus.     

Adenylate cyclase coupled beta adrenergic receptors of Rauscher erythroleukemia cells

Rauscher murine erythroleukemia cells undergo erythroid differentiation in response to the hormonal inducer erythropoietin and to synthetic inducers. Incubation of these cells with (?) isoproterenol or (?) epinephrine results in a 2–3-fold increase in cyclic AMP levels. This effect is completely blocked by propranolol, identifying the response as due to a β-adrenergic receptor·adenylate cyclase system. Experiments with [¹²⁵I]iodohydroxybenzylpindolol demonstrate 1700 β-adrenergic receptors/cell with a K_D of 320 pM. These results form the basis for further studies of the β-adrenergic receptor·adenylate cyclase complex during erythropoiesis.     

Alpha and beta adrenergic receptors of canine lung tissue identification and characterization of alpha adrenergic receptors by two different ligands

Adrenergic receptors of canine peripheral lung tissues were measured by direct binding techniques using [³H]dihydroergocryptine ([³H]DHE), [³H]prazosin and [³H]dihydroalprenolol ([³H]DHA). All three ligands bound to canine lung tissue with saturability, stereospecificity and reversibility. Adrenergic agonists competed for binding of [³H]DHE and [³H]prazosin in the order: 1-epinephrine > 1-norepinephrine > d-epinephrine > d-norepinephrine > 1-isoproterenol. Adrenergic antagonists competed for binding of [³H]prazosin in the order: prazosin > phentolamine > yohimbine. Inhibition curves of [³H]DHE by prazosin or yohimbine were biphasic suggesting two subtypes of binding sites. Maximum binding capacities of [³H]DHE ranged from 30.6 to 42.7 fmol/mg protein. [³H]prazosin from 18.3 to 26.9 fmol/mg protein and [³H]DHA from 135.2 to 359.4 fmol/mg protein. When both [³H]DHE and [³H]prazosin were used in the same membrane preparation, specific binding of [³H]DHE was always more than that of [³H]prazosin. Since [³H]prazosin is considered to bind to alpha₁ adrenergic receptors specifically and [³H]DHE is considered to bind alpha₂ adrenergic receptors nonselectively, the difference between the numbers of the specific binding sites of these two ligands should represent alpha₂ adrenergic receptors. Alpha₂ adrenergic receptor density ranged from 9.5 to 21.1 fmol/mg protein. Our results suggest the existence of both alpha₁ and alpha₂ adrenergic receptors in canine peripheral lung tissue. Approximately 40% of alpha adrenergic receptors were alpha₂. The ratio of alpha/beta adrenrgic receptors ranged from 1:3.3 to 1:10.4. The ratio of alpha₁/be ta adrenergic receptors ranged from 1:6.7 to 1:21.1.     

Influence of alpha and beta adrenergic receptors blockade on the adrenolytic effect of muscular work

The changes in the response of adrenergic receptors alpha and beta in the blood vessels in the working muscles in a hindlimb in cats were studied after intra-arterial administration of noradrenaline, isoprenaline and during electric stimulation of the sympathetic trunk. The experiments were carried out during alpha-adrenergic receptors blockade with dihydroergotamine (0.3 mg/kg) beta-adrenergic receptors blockade with propranolol (1 mg/kg) and blockade of acetylcholine M receptors with atropine (0.5 mg/kg). The investigations were performed at rest, during exercise (electric stimulation of the sciatic nerve) and after the exercise. The following results deserve attention: 1) beta-adrenergic receptors blockade reduced significantly the alpha-adrenolytic effect of exercise restoring the ability of blood vessel to constriction in response to noradrenaline; 2) the vasodilator effect of isoprenaline evident in resting state and maintained to some extent during exercise was abolished completely by preceding alpha-adrenergic blockade. The changes in the reactivity of resistance vessels in working skeletal muscles to noradrenaline, with abolition of its vasoconstrictor effect, have been shown by Rein [7] and others authors [2, 5]. Similarly, it is well known that the resistance vessels contain two types of adrenergic receptors alpha and beta, and that the response of the vessels to stimulation of these receptors are different [1]. In view of the recently published observations of Jarhult and Lundvall suggesting that the beta-adrenergic receptors play an important physiological role [6] in the arterial part of the microcirculation [6] and in view of the hypothesis put forward by Kunos and Szentivanyj that alpha and beta receptors can be transformed depending on the intensity of tissue metabolism [8] it seemed worth while to study more systematically the changes of the reactivity of alpha and beta adrenergic receptors in the vascular bed of the skeletal muscles during and after muscle exercise.     

Reduction of exercise inudced hyperventilation by blocking beta adrenergic receptors]

In normal subjects, beta-adrenergic blockage by propranolol or pindolol reduces exercise hyperventilation (40 to 60% VO2 max).     

Interaction of alpha and beta adrenergic stimulation on aortic ornithine decarboxylase activity

The interaction between beta and alpha adrenergic agonists on regulation of cockerel aortic ornithine decarboxylase (ODC) activity was examined. The beta adrenergic agonist isoproterenol both reduced basal aortic ODC activity and prevented induction of the decarboxylase by the alpha adrenergic agonist methoxamine. 3-Isobutyl-1- methylxanthine (IBMX) similarly reduced basal ODC activity and blocked induction of the enzyme by methoxamine. When given ten minutes before or after methoxamine, isoproterenol prevented aortic ODC induction, but not large sustained increases in blood pressure evoked by the alpha adrenergic agonist. In contrast, when injected three hours after methoxamine, isoproterenol had no effect on already elevated levels of enzyme activity. Addition of isoproterenol (10(-7)M), IBMX (1 mM) or dibutyryl cAMP (2.5 mM) to isolated aortic segments cultured in minimal salts-glucose media evoked decreases in basal levels of ODC activity resembling those observed in the intact animal. These results suggest that the balance between alpha and beta adrenergic stimulation may be an important feature of the regulation of polyamine biosynthesis in artery wall cells.     

Separation of solubilized alpha and beta adrenergic receptors by affinity chromatography.

Isoelectric focusing in the presence of Nonidet P-40 splits human chromatographically pure γ globin chains into two bands of isoelectric points 6.95 and 6.85, respectively. The comparison of the relative proportions of the two bands with the ratios between the G_γ and A_γ non allelic chains of human fetal hemoglobin suggests that the band at pI 6.95 corresponds to G_γ and the band at pI 6.85 corresponds to the A_γ chain; the latter is the only band present in a patient with Greek type hereditary persistence of fetal hemoglobin, producing only A_γ chains. Fluorography of electrofocusing-separated radioactive γ globin chains synthesized by thalassemic reticulocytes indicates that the relative $\text{G}{}_{\mathrm{\gamma }}\text{A}{}_{\mathrm{\gamma }}$ synthetic ratios are similar to the relative amounts of G_γ and A_γ chains accumulated in the erythrocytes, suggesting that the activities for the G_γ and A_γ mRNAs decay at roughly similar rates.     

Effect of beta adrenergic receptor agonists and blockaders on the action of bradykinin

A study was made of the effect of beta-adrenomimetics (isoprenaline, orciprenaline, inoline) and beta-adrenoblockers (propranolol, pindolol, oxprenolol, atenolol and practolol) on changes in the tone of smooth muscles of an isolate ileum of guinea-pigs, increase in microvascular permeability and depressor reaction in rats induced by bradykinin. beta-Adrenomimetics decreased spasmogenic and microcirculatory effects of bradykinin. Depending on the selectivity and presence of partial agonistic activity, beta-adrenoblockers exerted different influence on changes in the tone of extravasal muscles and permeability induced by bradykinin. In doses of 0.1, 0.5 and 1 mg/kg (intravenously) beta-adrenoblockers potentiated and prolonged the depressor effect of bradykinin.     

Comparative expression of the human beta(2) and beta(3) adrenergic receptors in Saccharomyces cerevisiae

The beta(3) adrenergic receptor (beta(3)AR) is the predominant beta subtype in human brown adipocytes and is essential for regulating thermogenic lipolysis. To establish a novel experimental system for the biochemical analysis of this protein, we engineered several yeast strains. We show that the sterol background of the host strain greatly modulates the beta(3)AR expression but not in the same way as it modulates the beta(2) adrenergic receptor (beta(2)AR), the other main studied adipocyte subtype. The human beta(3)AR expressed in yeast is N-glycosylated but not phosphorylated. This latter characteristic distinguishes it from the beta(2)AR. We showed that both beta(2)AR and beta(3)AR follow the secretory pathway to the yeast plasma membrane (PM) and are degraded in the vacuole. In the yeast strains used in this work, the two receptors also share a common mechanism of direct signal transduction through the yeast G(alpha) protein, Gpa1p. These strains thus appear to be useful for biochemical and structural studies of the human beta(3)AR in an in vivo reconstitution system.