https://www.jbc.org/content/247/4/1106.full.pdf

Radioimmunoassay for Cyclic Nucleotides I. PREPARATION OF ANTIBODIES AND IODINATED CYCLIC NUCLEOTIDES

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)

One of the important regulating factors in the control of a number of cellular processes appears to be the intracellular level of adenosine 3', 5'phosphate (cyclic AMP).'-3 The level of this chemical depends upon the relative activities of a t least two enzymes, viz., adenyl c y c l a ~ e , ~ which catalyzes the conversion of ATP to cyclic AMP, and a phosph~diesterase,~ which catalyzes the breakdown of cyclic AMP to 5'-AMP. Many of the actions of a number of hormones and neurohumors are now thought to be related to the ability of these agents to alter the intracellular level of cyclic AMP in their respective target cells, either by increasing the activity of adenyl cyclase or perhaps, in some cases, by an opposite effect on the cyclase or by an effect on the phosphodiesterase. T A B L E 1 contains a list of those hormones and neurohumors for which there is some evidence that this is the case. The resultant effect of the altered concentration of cyclic AMP will depend on the enzymatic profile of the particular cell type involved. The target systems on which cyclic AMP acts to produce the responses to the hormones listed in T A B L E 1 are not known in all cases. The effects which cyclic AMP can elicit, however, as they are known a t the present time, are summarized in T A B L E 2. It will be noted that these effects have been measured a t various different levels of organization, hence need not in all cases be mutually exclusive. The hormonal sensitivity of adenyl cyclase has been found to differ strikingly from tissue to tissue. Thus, for example, in the corpus luteum, cyclic AMP levels are increased by LH but not by ACTH, whereas in the adrenal cortex the reverse situation has been found to apply. Some tissues are highly specific, whereas in others, such as adipose t i s ~ u e , ~ ~ * ~ ~ a large number of hormones have been found to be active. The particulate nature of adenyl cyclase in most tissues, together with its lability (especially as regards hormonal sensitivity), have combined to make the purification and study of this enzyme difficult. Little is therefore known, in chemical terms, about the reasons for the hormonal specificity in different tissues. The enzyme appears to behave in most tissues as a l i p ~ p r o t e i n \" ~ and may be intimately associated with the lipid matrix of the cell membrane.40 One possible model of the adenyl cyclase molecule, which may be useful as a working hypothesis, is illustrated in FIG-

Adenyl cyclase as an adrenergic receptor

https://science.sciencemag.org/content/sci/177/4047/401.full.pdf

Studies on the mechanism of hormone action

Effects of lipolytic and antilipolytic substances on adenosine 3',5'-monophosphate levels in isolated fat cells.

Adenosine 3',5'-monophosphate in biological materials. II. The measurement of adenosine 3',5'-monophosphate in tissues and the role of the cyclic nucleotide in the lipolytic response of fat to epinephrine.

H.C. Meng

Papers

Adenosine 3',5'-monophosphate in biological materials. II. The measurement of adenosine 3',5'-monophosphate in tissues and the role of the cyclic nucleotide in the lipolytic response of fat to epinephrine.

Properties of intestinal lipase.