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A Goldfien

Publications and source records attributed to A Goldfien.

At least 37 records · Page 2Linked to original sources

Phaeochromocytoma.

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Adrenal Gland Neoplasms↗

Identification of beta-adrenergic receptors using [3H]dihydroalprenolol in fetal sheep heart: direct evidence of qualitative similarity to the receptors in adult sheep heart.

The fetal sheep heart responds to beta-adrenergic stimuli; however, in vivo studies show the response of the fetal heart is less than that of the adult heart. We used [3H]dihydroalprenolol (DHA) to study directly beta-adrenergic receptors in heart particulates of fetal sheep at term and adult sheep. [3H]DHA binding to fetal heart particulates was rapid, reversible (t 1/2 = 2.9 +/- 0.3 min), stereoselective, saturable (101.2 +/- 7.4 fmoles/mg protein), and of high affinity (4.8 +/- 0.4 nM). The rank order of agonists competing for [3H]DHA binding was isoproterenol (0.32 +/- 0.10 microM) greater than epinephrine (1.19 +/- 0.23 muM) approximately equal to norepinephrine (2.67 +/- 0.69 muM), which is compatible with beta 1-adrenergic potencies. [3H]DHA also bound to the adult sheep heart in a manner expected for beta 1-receptors. No difference in the binding affinity of [3H]DHA or agonists' competition was demonstrated between the fetal and adult sheep heart. Comparison of the concentration of beta-adrenergic receptors in fetal and adult hearts was confounded by the choice of the denominator for unit expression. The concentration was higher in the adult when expressed as a function of protein content or 5'-nucleotidase activity (0.52 +/- 0.07 versus 1.12 +/- 0.06). However, there was no difference when tissue weight, Na+ - K+-ATPase, or NaF-stimulated adenylate cyclase was used. Furthermore, isoproterenol-stimulated adenylate cyclase and cardiac contractile response to a threshold dose of isoproterenol were identical in the fetal and adult sheep heart. We conclude that beta-receptors can be studied with [3H]DHA in the fetal sheep heart, this receptor is qualitatively similar to the beta-receptor in the adult sheep heart, and it is unlikely that there is a difference in the concentration of beta-adrenergic receptors in fetal and adult sheep heart.

Adenylyl Cyclases↗

Decreased concentration of myocardial alpha-adrenoceptors with increasing age in foetal lambs.

Using [3H]-dihydroergocryptine, we identified myocardial alpha-adrenoceptor binding sites in foetal lambs and demonstrated that the concentration of receptors decreased with increasing foetal age. The presence of the receptor in the foetus correlated with the presence of myocardial alpha-adrenergic responsiveness. However, we found neither the alpha-receptor binding site nor responsiveness to alpha-adrenoceptor stimulation in the myocardium of adult sheep.

Animals↗

Glucocorticoids increase pulmonary beta-adrenergic receptors in fetal rabbit.

beta-Adrenergic agonists stimulate surfactant release and decrease fluid in lung alveoli of fetuses. Both effects are most evident toward the end of gestation. We used [3H] dihydroalprenolol (DHA) to investigate the development of pulmonary beta-adrenergic receptors in rabbit fetuses and to study the effect of glucocorticoid treatment on the beta-receptor number. In the lung particulate preparation, DHA binding was rapid, reversible, stereoselective, and of high affinity. The order of potency for adrenergic agonists in competing for DHA binding was isoproterenol > epinephrine = norepinephrine, which is typical of interactions at a beta 1-adrenergic receptor. Using DHA, we demonstrated that the concentration of pulmonary beta-receptors increased significantly between 28 and 31 days of gestation; however, there was no change in the dissociation constant during gestation. After injecting betamethasone (0.17 mg/kg, 24 hours) into rabbits at 25 days of pregnancy, we found that the concentration of pulmonary beta-receptors increased from 44.2 +/- 6.6 fmol/mg protein in untreated fetuses to 77.9 +/- 5.6 fmol/mg protein in treated fetuses. However, this treatment did not affect the DHA binding sites in the fetal rabbit heart. Maternal treatment with the T3 analogue 3,5-dimethyl-3'-isopropyl-L-thyronine (0.5-1 mg/kg) at a dosage which increased both surfactant synthesis and release did not alter pulmonary receptor concentration. Our results indicate that the concentration of pulmonary beta-adrenergic receptors increases in the fetus at term and suggest that this increase is stimulated by endogenous glucocorticoid in fetal circulation.

Animals↗

Identification of beta-adrenergic binding sites in rabbit myometrium.

Rabbit uterine muscle may contract or relax with adrenergic stimulation depending on the hormonal milieu. This difference in contractile activity has been shown to be due to alteration of adrenergic response between alpha-adrenergic (contraction) and beta-adrenergic (relaxation). When rabbits are treated with estrogen followed by progesterone, norepinephrine produces myometrial relaxation. This effect is blocked by propranolol, indicating that it is mediated by beta receptor activation. A subcellular preparation of this myometrium has adenylate cyclase activity that can be stimulated by isoproterenol + guanyl-5'-yl-imidodi-phosphate (Gpp(NH)p). The radioligand [125I]iodohydroxybenzylpindolol binds to the same preparation. The binding is rapid, 80% maximal in 10 min, and readily reversible (t1/2 = 5 min). The binding is high affinity (Kd = 0.12 nM), low capacity (15 fmol/mg protein), and is to a single class of binding sites. Binding is competed for stereoselectively by beta adrenergic agonists and antagonists. The competition of beta adrenergic agonists for binding, isoproterenol = ritodrine greater than epinephrine greater than norepinephrine, is consistent with interactions at a beta2-adrenergic receptor.

Adenylyl Cyclases↗

Reversible norepinephrine binding to rabbit myometrium: relationship to sites of known biological significance.

Catecholamines bind specifically to several cell types and subcellular fractions. This binding is not consistent with binding to the adrenergic receptor. Catecholamines would be expected to bind to sites other than the adrenergic receptor (uptake 1, uptake 2, nerve vesicles, catecholamine-O-methyl transferase and serum albumin). We characterized the binding of 3H-norepinephrine to microsomes prepared from rabbit myometrium. In the presence of antioxidant binding was reversible and 3H-norepinephrine could be recovered bound to microsomes or free in incubation media. The binding was not characteristic of binding to any one known biological site. It may represent binding to a mixture of these sites or may be fortuitous binding to sites of unknown biological significance.

Animals↗

Possible mechanism for the antiarrhythmic effect of helium in anesthetized dogs.

Breathing a mixture of 75 percent helium and 25 percent oxygen instead of 75 percent nitrogen and 25 percent oxygen reduced the occurrence of dangerous cardiac arrhythmias after ligation of the circumflex coronary artery in open-chest dogs anesthetized with pentobarbital. In dogs not subjected to circumflex ligation, the sensitivity of blood pressure, heart rate, and extrasystoles to epinephrine injected intravenously was not altered by the substitution of helium for nitrogen; however, helium did reduce the baseline heart rate and the concentration of endogenous plasma catecholamines. The antiarrhythmic effect of helium may thus be mediated by changes in sympathetic activity.

Anesthesia, General↗