The initial concept that cyclic AMP is an intermediate in the actions of glucagon and epinephrine has evolved rapidly to include an array of biologi cal phenomena so extensive that virtually every facet of pharmacology is now involved. Hundreds of relevant publications have been reviewed re cently (1-3), and a monograph on cyclic AMP is forthcoming (4) . Valu able accounts of cyclic AMP effects are available pertaining to polypeptide hormones (5), diazoxide (6), skeletal muscle (7), prostaglandins (8), and insulin secretion (9). It is conceivable that the biological effects of mate rials as diverse as cardiotonic, psychotropic, contraceptive, antibiotic, and diuretic agents will be understood soon in terms of cyclic AMP action. At present our limited insight into the cyclic AMP-related actions of drugs is the result of our imperfect knowledge of cyclic AMP function at the cellu lar level. Understanding of cyclic AMP-linked drug effects probably will be attained in terms of the mechanisms of action of the cyclic nucleotide and the means by which its intracellular concentration is controlled. Therefore, the enzymes of cyclic AMP metabolism and certain basic cell functions have been selected as topics under which to summarize research published, with few exceptions, subsequent to previous reviews. Included are substantial ad ditions to the evidence which supports the concept formulated by Sutherland and his colleagues of cyclic AMP as a second messenger. A few reports sug gest that the momentum for general acceptance of that exceedingly useful thesis is so great that other possible interpretations may be obscured.
ADENYL CYCLASERecent studies are in accord with earlier work in showing enzyme activ ity to be associated with particles, to have moderately alkaline pH optima, and to be stimulated by magnesium and fluoride (10-15). A soluble cyclase from E. coli has been purified IOO-fold (16). Fluoride inhibits this enzyme, as well as partially purified cyclase from liver (17) and adipose cells (18). The presence of functional sulfhydryl groups may be inferred from the re quirement for dithioerythrotol in frog erythrocytes (14). The apparent Km for ATP is about 1 X lO-4M in the presence of fluoride in pineal body (11) 1 Abbreviations used in this review are: cyclic AMP (adenosine 3',5' -mono phosphate); db-cyclic AMP (NB,2'-O-dibutyryl adenosine 3',5'-monophosphate); MJ1999 (4-(2cisopropyIamino-l-hydroxyethyl) methanesulfonanilide HeI).