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By Bernard L. Horecker, Earl R. Stadtman, P. Boon Chock

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2+ and As described above, in the case of both K and ACTH, C a cAMP serve as coordinate messengers in mediating the sustained responses to these extracellular signals. On the other hand, an increase in cAMP concentration acts as an inhibitor of Ang II-stimulated P I P 2 hydrolysis (Woodcock, 1989). Hence, when ACTH acts together with Ang II, there is a decrease in signal generation in the two branches of 2+ the C a messenger system, but an increase in the efficiency of readout of the messages in each of the two branches.

The sustained phase, mediated by the C kinase branch, lasts for hours. A particularly important discovery is the recognition t h a t an in2+ 2 + crease in C a cycling, and a consequent increase in [ C a ] s m , is a key messenger during the sustained phase of the response. Inhibition of this 2+ increase in C a cycling inhibits the response. , aldosterone secretion and insulin secretion, this feature provides a means by which a fail-safe mechanism operates in a physiologic system to prevent the inappropriate secretion of the particular hormone under conditions where such a secretion could be detrimental 2+ to the organism.

1975; Butcher, 1975; Schultz and Hardman, 1975). However, in one system, vascular smooth muscle, there is considerable recent evidence linking increases in intracellular [cGMP] to relaxation. , 1989). It has been proposed t h a t this relaxing effect of cGMP is mediated by cGMPdependent protein kinase (G kinase). , 1984; F u r u k a w a and Nakamura, 1987; Furukawa et al, 1988). Supporting this hypothe2+ sis is the demonstration of a stimulation of C a - d e p e n d e n t ATPase activity (a decrease in Km and increase in V m a x ) by cGMP in plasma 2+ CALCIUM AS INTRACELLULAR MESSENGER 31 membrane-enriched fractions from smooth muscle as well as in the solubilized plasmalemma.

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