beta 2 adrenoreceptor desensitization

1 The formation and release of PGE2-like material (PGE2-lm) from guinea-pig isolated trachea and human bronchi following relaxation with isoprenaline (I) was investigated. 2 When airway smooth muscle precontracted with pilocarpine is relaxed by I, PGE2-lm is released in the bathing fluid. Under conditions of beta-adrenoreceptor desensitization, a greater amount of PGE2-lm is formed and the responsiveness of guinea-pig tracheal spirals to cumulative doses of I is diminished. 3 Inhibition of cyclo-oxygenase with indomethacin does not modify the relaxation induced by I but prevents the occurrence of refractoriness to I as well as formation and release of PGE2-lm...

Long-term exposure of pigeon erythrocytes to isoproterenol causes substantial changes in the regulatory properties of adenylate cyclase. The enzyme sensitivity to isoproterenol (0.2 mM) and GTP (1.0 mM) decreases by 50% after 20 min incubation, while that to guanylyl imidodiphosphate (0.1 mM), a non-hydrolyzeable analogue of GTP, is lowered by 20-25% after 40 min. The decrease of the enzyme sensitivity to the activators is associated with the appearance of a lag period in the effects of isoproterenol and Gpp(NH)p and with an increase of the lag period in the effect of Gpp(NH)p...

1. In conscious cats prepared with gastric fistulae gastric acid secretion in response to pentagastrin was found to reach a maximum after 45 min of stimulation, and to fade thereafter. Over the period 45-150 min of stimulation the fade was 5.4-7.8% of the maximum response per 15 min. 2. Once the response to pentagastrin had declined, acid secretion could not be restored by doubling the dose of pentagastrin, although an equisecretory dose of histamine could restore it. 3. Low doses of histamine were additive to the pentagastrin acid secretory response; they tended to prolong the peak response, but did not alter the subsequent fade of acid secretion...

The number of beta-receptors was determined in 60 atopic patients: 30 asthmatics with sensitization to domestic inhalant allergens and 30 rhinitic patients with sensitization to pollen and/or Dermatophagoides antigens. A L-iodocyanopindolol radio-active marker was used. Our control population (20 healthy individuals) showed 908 +/- 396 receptors/cell. The rhinitic individuals showed a 24% decrease in receptors in relation to the control population. On the other hand, within the asthmatic patients there existed 2 differentiated groups: inactive asthmatics whose receptors were found to be within the normal limits and active asthmatics with a 36% decrease in receptors in relation to the healthy individuals (673 receptors/cell) establishing a significant statistical difference (p less than 0...

A new procedure is presented that characterizes the specific binding of the beta-adrenergic antagonist, [3H]CGP-12177, to thick (1 mm) slices from fast-twitch [extensor digitorum longus (EDL)] and slow-twitch (soleus) mouse skeletal muscle. Binding is reversible, saturable, stereospecific, of high affinity, and subject to agonist-induced desensitization, indicating that it is to beta-adrenoreceptors and not to other sites. In both muscles, the majority of specific binding is to the beta 2-receptor subtype. Bmax is approximately twice as high in the soleus (5...

Effect of desensitization of alpha-adrenoreceptors on the functional state of beta-receptors and vice versa was studied in isolated sections of the rat small intestine. Neither blockade, nor desensitization of alpha-receptors produced any effect on the sensitivity of beta-receptors to isopropyl-noradrenaline (IPN) whereas desensitization of beta-receptors to IPN resulted in the increase of alpha-receptors sensitivity to phenylephrine with a decreased maximal reaction. In the presence of GTP (0.02 mM) and propranolol (2...

27 patients with dilated cardiomyopathy (DCM) complicated by heart failure (HF) of stages I-IIB were studied. The density of lymphocyte beta 2-adrenoceptors decreased significantly as HF progressed. The level of circulating catecholamines (epinephrine, norepinephrine) was significantly higher in patients were severe HF, which probably caused more evident decrease in lymphocyte beta 2-adrenoceptors density in these patients. This point of view was confirmed by the data of correlation-regression analysis between the general beta 2-adrenoceptors density and hemodynamics data...

The foetal lung responds to beta-receptor agonists with a release of surfactant from alveolar cells. The aim of the present study was to investigate whether the administration of the betamimetic fenoterol could influence the desensitization - associated decrease of beta-adrenoreceptors in the rabbit foetal lung. With experiments on pregnant rabbits, this hypothesis was put to the test and found to be true. At a gestational age of 27-28 days, does were infused 7.5-10.0 mg of fenoterol or given Ringer's solution...

1. In pithed rats, the blood pressure effects of ATP, alpha,beta-methylene ATP (mATP), alpha-adrenoreceptor agonists and of electrical stimulation of the thoracolumbar sympathetic outflow were studied in the absence and presence of mATP, suramin and adrenoreceptor antagonists. 2. ATP elicited an initial rise in mean blood pressure followed by a decrease and a second increase. mATP produced a short-lived increase in blood pressure, whereas equieffective doses of noradrenaline, methoxamine and B-HT 920 (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-(5,4-d)-azepine) produced a more prolonged, biphasic pressor response...

High-altitude pulmonary arterial hypertension affects people with a long-term residence at altitudes over 2500 m above the sea level and is characterized by elevated pulmonary artery pressure (over 35/15 mmHg). In order to assess the role of beta-adrenoreceptors in the development of high-altitude pulmonary arterial hypertension, we studied the beta-adrenoreceptor density on mononuclear leukocytes in Kirghiz male natives of Eastern Pamir (3600-4200 m above sea level) with the diagnosis of high-altitude pulmonary arterial hypertension, and in healthy men...

Twenty eight males with dilated cardiomyopathy, 5 males with coronary heart disease concurrent with postinfarction cardiosclerosis, 4 males and 2 females with rheumatic heart disease were examined. The findings suggest desensitization of the cellular beta-adrenoreceptor complex in patients with circulatory failure, which appeared as lower beta-adrenoreceptor density with cardiac decompensation progression and impaired transmission of a hormonal signal in the cell, particularly in patients with dilated cardiomyopathy...

In neuroleptic therapy for psychotic illnesses, clinical improvement occurs much later than central dopamine blockade, and its time course varies widely among patients. A hypothesis explaining neuroleptic-responsive illness cannot be explained by dopamine blockade alone. Nevertheless, experimental data suggest that this mechanism may be a step in the therapeutic process for schizophrenia. Explanations are suggested for the time lag in therapeutic response for neuroleptics, including the hypothesis of delayed inactivation of mid-brain dopamine neurones...

By studying the effects of oxygen deficiency upon signal-transducing system it has been shown that in long hypobaric hypoxia activates PI-turnover in cultured human endothelial cells. The sensitivity of cells to histamine was decreased as well as the adenylate cyclase activity in membranes of this cells. The amount of beta-adrenoreceptors was not influenced significantly. Incubation of endothelial cells with histamine (10(-5) M) and phorbol ester (10(-9) M) = activator of protein kinase C within 1-2 h resulted in desensitization of cellular responses which can be seen not only as a disappearance of histamine-induced activation of PI-turnover but also as a decrease of beta-adrenoreceptor amount and adenylate cyclase activity...

The present work was undertaken to characterize the role of serotonin in the regulation of beta-adrenoceptors utilizing isoprenaline-induced water drinking in the rat. For this purpose, a serotonin precursor, 5-hydroxytryptophan (24.3 mg/kg/day, PO), the serotonin neuronal uptake blockers, trazodone (18.5 mg/kg/day, PO), or zimelidine (14.6 mg/kg/day, PO) or a serotonin agonist, quipazine (12.6 mg/kg/day, PO) were administered either alone or in combination with imipramine for a period of 4 days. While none of these drugs alone showed any significant effect in attenuating the effects of isoprenaline-induced water drinking, their co- administration with imipramine did produce a significant reduction in isoprenaline-induced drinking...