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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Central and regional haemodynamics and leg metabolism at rest, during and after a prolonged exercise were studied in seven untreated hypertensive males before and after a long-term treatment (6 weeks) with an unselective beta-receptor-blocking drug (alprenolol). 2. Alprenolol treatment (200-400 mg, twice daily) decreased arterial blood pressure at rest and during exercise; it reduced heart rate in relation to drug plasma concentrations during and after exercise; it left cardiac output unchanged; it reduced leg blood flow at rest, but had no effect on leg blood flow during exercise. 3. Alprenolol treatment also decreased lipolysis and lactate release in relation to drug plasma concentrations during exercise.
Clin Sci Mol Med Suppl 1976 Dec
PMID:Effect of long-term anti-hypertensive beta-receptor-blocking treatment on haemodynamic and metabolic responses to prolonged exercise in man. 107 68

[3H]Dihydroalprenolol ([3H]DHA) has been used extensively in receptor binding studies to measure beta-adrenergic receptors in the central nervous system. Usually, nonspecific binding has been defined by high concentrations of the beta-adrenergic receptor agonist isoproterenol or antagonists such as alprenolol or propranolol. Scatchard plots of such "specific" [3H]DHA saturation data in rat cerebral cortex membranes are linear. However, computer analysis demonstrated that the competition curves of these drugs for 2.0 nM [3H]DHA binding are biphasic, with a continuous inhibition of [3H]DHA binding in the concentration range usually used to determine nonspecific binding. These data indicate that another saturable high affinity site was being labeled by the radioligand and that the definition of nonspecific binding with any of these unlabeled drugs is not satisfactory. We used the nonlinear, least squares, curve-fitting program LIGAND to analyze total [3H]DHA binding, allowing the program to mathematically define nonspecific binding as a function of 3H-ligand concentration. Significantly lower Bmax (-44%) and Kd (-58%) values for beta-adrenergic receptors were found, indicating that under normal experimental procedures (defining [3H]DHA non-specific binding with these nonradioactive drugs) a second binding site was being labeled. We found that [3H]DHA binding to this site could be inhibited by drugs such as RU24969, a 5-hydroxytryptamine1A (5HT1A) and 5HT1B receptor subtype-selective agonist, and CGS12066B, a 5HT1B receptor subtype-selective agonist, which were able to compete for 15-20% of [3H]DHA binding in the nanomolar concentration range, whereas drugs that are selective for other serotonin receptor subtypes inhibited [3H]DHA binding only at much higher concentrations. Another beta-adrenergic receptor antagonist radioligand, [3H]CGP-12177, was found to be more selective for beta-adrenergic receptors. Alprenolol competition curves for [3H]CGP-12177 binding were monophasic and saturation curves, with nonspecific binding defined either by 10 microM alprenolol or by LIGAND, yielded Bmax values close to those obtained with [3H]DHA when its nonspecific binding was defined by LIGAND. [3H]DHA cannot be considered a suitable radioligand to quantify central nervous system beta-adrenergic receptors in the manner in which it has been typically used.
Mol Pharmacol 1989 Jul
PMID:Comparison of two putatively selective radioligands for labeling central nervous system beta-adrenergic receptors: inadequacy of [3H]dihydroalprenolol. 254 50

Endothelin (ET)-1 is the prototype of a family of 21-amino acid residue hypertensive peptides, acting through two subtypes of receptors, named ETA and ETB. ETs and their receptors are expressed in the adrenal cortex and medulla, and ET-1 enhances both corticosteroid and catecholamine release. ET-1 concentration-dependently (from 10(-11) to 10(-8) M) increased aldosterone secretion of both dispersed rat zona glomerulosa (ZG) cells and adrenal slices containing a core of medullary chromaffin tissue, but the response of the latter preparations was significantly more intense than that of the formers. The stimulatory effect of 10(-8) M ET-1 on dispersed ZG cells was blocked by the ETB-receptor antagonist BQ-788 (10(-7) M), but not by the ETA-receptor antagonist BQ-123 (10(-7) M); conversely, both ET-receptors antagonists counteracted aldosterone response of adrenal slices to ET-1. The -adrenoceptor antagonist l-alprenolol (10(-6) M) did not affect aldosterone response of dispersed ZG cells to ET-1 (10(-8) M), but it significantly lowered that of adrenal slices. l-Alprenolol also counteracted the aldosterone response of adrenal slices to the pure activation of ETB or ETA receptors, as obtained by using the selective ETB-receptor agonist BQ-3020 (10(-8) M) or ET-1 (10(-8) M) plus BQ-788 (10(-7) M). ET-1 concentration-dependently (from 10(-9) to 10(-8)/10(-7) M) stimulated catecholamine release by adrenal slices, and the effect was counteracted by both BQ-123 and BQ-788 (10(-7) M). Collectively, our findings suggest that, when the integrity of adrenal tissue is preserved, a two-fold mechanism underlies the aldosterone secretagogue action of ET-1 in the rat: i) a direct mechanism mediated by ETB receptors located on ZG cells; and ii) an indirect mechanism involving the ETA and ETB receptor-mediated local release of catecholamines, which in turn stimulate ZG cells in a paracrine manner.
Int J Mol Med 1999 Mar
PMID:Mechanisms and receptor subtypes involved in the stimulatory action of endothelin-1 on rat adrenal zona glomerulosa. 1002 57

There are three members of the beta-adrenoceptor family, all of which are primarily coupled to G(s) proteins. Recent studies using the huge range of beta-ligands now available have given remarkable new insights into their pharmacology. beta1-adrenoceptors exist in at least two active conformations, whereas beta2-adrenoceptors are able to induce signaling via different agonist-induced receptor conformational states, and their affinity for antagonists can be altered by highly efficacious agonists. This study therefore examined the pharmacology of the human beta3-adrenoceptor stably expressed in Chinese hamster ovary cells. Several compounds described previously as beta-antagonists have agonist properties at the beta3-adrenoceptor. Antagonist affinity measurements varied at the beta3-adrenoceptor in a manner similar to those observed at human beta1-adrenoceptors and unlike those seen at beta2-adrenoceptors. Some ligands (e.g., fenoterol and cimaterol) were more readily inhibited by all antagonists, whereas other ligands [e.g., alprenolol and 1-(2-ethylphenoxy)-3-[[(1S)-1,2,3,4-tetrahydro-1-naphthalenyl]amino]-(2S)-2-propanol hydrochloride [SR 59230A]) stimulated responses that were more resistant to antagonism. Alprenolol inhibited fenoterol-induced beta3-adrenoceptor responses while acting as an agonist at higher concentrations. This is highly suggestive of two active conformational states of the beta3-adrenoceptor. (S)-4-[2-Hydroxy-3-phenoxypropylaminoethoxy]-N-(2-methoxyethyl)phenoxyacetamide (ZD 7114) stimulated a two-component response, of which the first component was more readily antagonized than the second. Taken together, these experiments suggest that the human beta3-adrenoceptor exists in at least two different agonist conformations with a similar high- and low-affinity pharmacology analogous to, if not as pronounced as, the beta1-adrenoceptor. Both conformations are present in living cells and can be distinguished by their pharmacological characteristics. In this respect, the human beta3-adrenoceptor seems similar to the human beta1-adrenoceptor.
Mol Pharmacol 2005 Dec
PMID:Evidence for a secondary state of the human beta3-adrenoceptor. 1612 33