https://pharmrev.aspetjournals.org/content/pharmrev/46/2/205.full.pdf

International Union of Pharmacology classification of prostanoid receptors: properties, distribution, and structure of the receptors and their subtypes.

We used radioligand binding techniques and measurement of beta-agonist-mediated positive inotropic responses in isolated cardiac tissue to examine beta-adrenergic-receptor subpopulations in nonfailing and failing human left and right ventricular myocardium. In tissue derived from 48 human hearts the receptor subtypes identified in nonfailing ventricle by radioligand binding were beta 1 (77%) and beta 2 (23%), with no evidence of an "atypical" beta-adrenergic receptor. In failing left ventricle the beta 1:beta 2 ratio was markedly different, i.e., 60:38. This decrease in the beta 1 proportion and increase in the beta 2 proportion in the failing ventricles were due to a 62%, "selective" down-regulation of the beta 1 subpopulation, with little or no change in beta 2 receptors. In muscle bath experiments in isolated trabeculae derived from nonfailing and failing right ventricles, both beta 1- and beta 2-adrenergic receptors were coupled to a positive inotropic response. In nonfailing myocardium, beta 1 responses predominated, as the selective beta 1 agonist denopamine produced a response that was 66% of the total contractile response of isoproterenol. In heart failure the beta 1 component was markedly decreased, while the beta 2 component was not significantly diminished. Moreover, in heart failure the beta 2 component increased in prominence, as the contractile response to the selective beta 2 agonist zinterol increased from a minority (39%) to a majority (60%) of the total response generated by isoproterenol. We conclude that failing human ventricular myocardium contains a relatively high proportion of beta 2 receptors, due to selective down-regulation of beta 1 receptors. As a result, in the failing human heart the beta 2-receptor subpopulation is a relatively important mediator of inotropic support in response to nonselective beta-agonist stimulation and is available for inotropic stimulation by selective beta 2 agonists.

Beta 1- and beta 2-adrenergic-receptor subpopulations in nonfailing and failing human ventricular myocardium: coupling of both receptor subtypes to muscle contraction and selective beta 1-receptor down-regulation in heart failure.

https://pharmrev.aspetjournals.org/content/pharmrev/46/2/121.full.pdf

International Union of Pharmacology nomenclature of adrenoceptors.

Since the discovery of renin 80 years ago, there have been remarkable advances in our understanding of the renin-angiotensin system. The system as it is known today is summarized in Figure 1. Angiotensin III, the active component of the system, has several important physiological actions. The first of these to be identified was its pressor action, and for many years it was felt that the sole function of the renin-angiotensin system was regula­ tion of blood pressure. A new dimension was added in 1960 with the discovery that angiotensin II stimulates the secretion of aldosterone and is therefore in a position to exert important effects on salt and water balance. Several additional actions of angiotensin II were then discovered. It was found that the peptide can increase the secretion of catecholamines from the adrenal and facilitate adrenergic transmission. It also acts directly on the brain to increase blood pressure via sympathetic and parasympathetic path­ ways, to produce thirst, and to stimulate the secretion of vasopressin and ACTH. Through these actions, the renin-angiotensin system plays an im­ portant role in the regulation of blood pressure and of the volume and composition of the extracellular fluid. Major advances have also been made in our understanding of other aspects of the renin-angiotensin system. It has become clear that the hep­ tapeptide metabolite of angiotensin II, [des-Aspl] angiotensin II ("angio-

The Renin-Angiotensin System

Cyclic AMP (adenosine 3',5'-monophosphate or cyclic adenylate) has now been established as a second messenger mediating many of the effects of a variety of hormones. Several of the metabolic effects mediated by cyclic AMP are discussed, and it is suggested that certain other ("functional" or "mechanical") hormonal effects may be similarly mediated. In particular, the evidence presented supports the hypothesis that the positive inotropic response to the catecholamines is mediated by cyclic AMP. Although knowledge of the biological role of cyclic AMP has not been widely applied clinically, sufficient knowledge has now accumulated to make research in this area desirable.

Some Aspects of the Biological Role of Adenosine 3',5'-monophosphate (Cyclic AMP)

CLASSIFICATION of receptor systems which are activated by sympathomimetic amines has engaged the attention of many investigators. Ahlquist1–3 has suggested the convenient designations of alpha (α) and beta (β) to distinguish major differences in the responses elicited in various organ systems. Our investigations have provided results which cannot be explained easily on the assumption that the β-type designates a single receptor population4–6. We now report additional studies which show that two distinct receptor types are at present included within this group.

J. P. Mcauliff

Papers

Differentiation of receptor systems activated by sympathomimetic amines.

Differentiation of receptor systems activated by sympathomimetic amines

The beta-2 receptor mediated glycogenolytic responses to catecholamines in the dog