Number Of Alpha 2-adrenergic Receptors Research Articles

Platelet α2-Adrenergic Receptors in Major Depressive Disorder

The specific binding of tritiated (3H)-clonidine, an alpha 2-adrenergic receptor agonist, to platelet membranes was measured in normal subjects and in patients with major depressive disorder. The number of platelet alpha 2-adrenergic receptors from the depressed group was significantly higher than that found in platelets obtained from the control population. Treatment with tricyclic antidepressant drugs led to significant decreases in the number of platelet alpha 2-adrenergic receptors. These results support the hypothesis that the depressive syndrome is related to an alpha 2-adrenergic receptor supersensitivity and that the clinical effectiveness of tricyclic antidepressant drugs is associated with a decrease in the number of these receptors.

Increased alpha-adrenergic receptors in ischemic cat myocardium. A potential mediator of electrophysiological derangements.

We have recently demonstrated enhanced alpha-adrenergic responsiveness assessed electrophysiologically in ischemic and reperfused myocardium. This study was performed to determine whether ischemia alters alpha 1-adrenergic receptor number (Bmax) of affinity (KD) based on [3H]prazosin binding. Within 30 min after occlusion, Bmax increased in ischemic regions to 207% of control to 27 +/- 2 fmol/mg protein, with the increase persisting (+ 141% of control) during early reperfusion (2 min), before returning to control base-line values (13 +/- 1.6) after 15 min of reperfusion. KD was not altered at any interval studied. Beta receptor number of ([3H]dihydroalprenolol) and Na+-K+ ATPase activity were comparable in control compared to ischemic myocardium although beta-receptor Bmax and KD in both regions decreased during early reperfusion. Thus, the enhanced alpha-adrenergic responsivity previously recognized with ischemia and reperfusion is correlated with an increase in alpha 1-adrenergic receptors.

Alpha 2-Adrenergic receptors appear in rat salivary glands after reserpine treatment.

The regulation of central and peripheral adrenergic receptors by various chemical, physiological, pharmacological and pathological stimuli has been the subject of intense study. For example, drug treatments can produce relatively small changes in the density of existing receptor binding sites in a variety of tissues. The alpha-adrenergic receptors in rat salivary gland tissue have been studied using radioligand receptor binding techniques. We have recently identified and characterised alpha 1-adrenergic receptors in the rat submandibular gland, but surprisingly, alpha 2-adrenergic receptor binding was not detectable. We now report that a single treatment of reserpine results in the appearance of alpha 2-adrenergic binding sites within 12 h. Continued treatment with the drug produces further increases in the number of alpha 2-adrenergic receptors, such that after 7 days the levels of alpha 1- and alpha 2-adrenergic receptors are similar. This is the first example of a drug treatment resulting in the appearance of a receptor type which was not previously detectable.

Thyroxine and Propylthiouracil Effects on Alpha- and Beta-Adrenergic Receptor Number, ATPase Activities, and Sialic Acid Content of Rat Cardiac Membrane Vesicles

Membrane vesicle preparations from the hearts of euthyroid, hyperthyroid, and hypothyroid rats were analyzed in an attempt to identify biochemical changes which might correlate with known functional changes occurring in these thyroid states. Several sarcolemmal constituents which have been shown to influence myocardial contractility were measured in membrane vesicle preparations from the hearts of animals in the three thyroid states. These constituents included the apparent number of alpha- and beta-adrenergic receptors (judged from specific binding of radiolabeled adrenergic antagonists) and Na-, K--ATPase activity. As a control for the recovery of sarcolemma in the preparations, the sialic acid content was measured in all preparations. The activity of K-, Ca2--ATPase, a sarcoplasmic reticulum enzyme which regulates intracellular ionized Ca2- concentration, was also measured. Membrane vesicles of the thyroxine-treated hyperthyroid rats showed a decrease (41%, p < 0.01) in the total apparent number of alpha-adrenergic receptors relative to euthyroid controls and an increase in the total apparent number of beta-adrenergic receptors (43%, p < 0.001). Membrane vesicles prepared from propylthiouracil-treated hypothyroid rats showed a decrease relative to euthyroid controls in the total apparent number of both alpha-adrenergic receptors (29%, p < 0.01) and beta-adrenergic receptors (23%, p < 0.05). The ratio of beta- to alpha-receptors approximately doubled in the hyperthyroid animals but remained unchanged compared to controls in the membranes isolated from hypothyroid animals. In the same membrane vesicle preparations, total sialic acid content was similar regardless of thyroid state. In addition.

Reduced cyclic AMP production in the blood platelets from schizophrenic patients

The authors assessed alpha-adrenergic receptor function in blood platelets from chronic schizophrenic patients and normal control subjects. The number of receptors was measured by the specific binding of the alpha-adrenergic antagonist [3H]dihydroergocryptine to the platelets. A physiological response of the platelets to agonist occupancy of the alpha-adrenergic receptors was measured by the norepinephrine inhibition of prostaglandin E1(PGE1)-stimulated cyclic AMP (cAMP) production. cAMP production in male schizophrenic patients was lower than in normal male subjects. alpha-Adrenergic receptor function was similar in patients and normal control subjects of both sexes. Normal male subjects had about 1.5 times the number of alpha-adrenergic receptors as normal females and generated about 1.8 times the quantity of PGE1-stimulated cAMP.

Adrenergic Receptor Function is Different in Male and Female Patients with Essential Hypertension

As plasma norepinephrine (NE) levels may be similar in hypertensive and normotensive subjects, the sensitivity of adrenergic receptors was investigated in patients with essential hypertension and normotensive subjects of similar age and sex. Alpha-adrenergic receptor sensitivity was measured in platelets by the specific binding of [3H]dihydroergocryptine and the NE inhibition of prostaglandin E1 (PGE1)-stimulated cyclic AMP (cAMP) production. The number of alpha-adrenergic receptors in platelets from hypertensive women was 1.5 times that in the platelets from normotensive ones, with no differences between hypertensive and normotensive women or between men and women in the affinity of the alpha-adrenergic receptor for [3H]dihydroergocryptine. PGE1-stimulated cAMP production was half as great in hypertensive as in normotensive men, while NE inhibition of PGE1-stimulated cAMP production was similar in hypertensive and normotensive men and women. [3H]Dihydroergoeryptine binding in female hypertensives, and PGE1-stimulated cAMP in male hypertensives did not differ from that in sex-matched controls. The sensitivity of the beta-adrenergic receptor, measured by [3H]dihydroalprenolol binding and cAMP production was similar in hypertensive and normotensive subjects.

Development of cardiovascular responses to sympathomimetic amines and autonomic blockage in the unanesthetized fetus.

The cardiovascular effects of phenylephrine or ephedrine alone and after autonomic blockade was studied in the chronically cannulated fetal lamb (100-145 days), the newborn lamb, and adult sheep. As gestation advanced, phenylephrine and ephedrine produced an increasing pressor response before and after pretreatment with atropine (1 mg/kg). Compared with the fetus, the magnitudes of the pressor responses were somewhat greater in the newborn and much larger in the adult. Both drugs produced a reflex bradycardia in the unatropinized fetus which in the case of ephedrine was followed by a tachycardia. Pretreatment with atropine resulted in an immediate tachycardia after ephedrine but not after phenylephrine administration. Pretreatment with phentolamine (0.15 mg/kg) produced about a 55% inhibition of the phenylephrine pressor response in both the fetus and adult, suggesting a linear relationship between body weight and number of alpha-adrenergic receptors. Pretreatment with metoprolol blocked the tachycardia associated with ephedrine administration to unatropinized fetuses. In summary, the increase in the magnitude of the pressor response to phenylephrine suggested development of the receptor-effector system. The greater development of the response to ephedrine suggested that there was an increasing amount of noradrenaline being released with advancing gestation.