The role of 5-hydroxytryptamine and cyclic AMP in the control of fluid secretion by isolated salivary glands.

The discovery of adenosine 3',5'-monophosphate (cyclic AMP) has provided a focal point for studies on the mode of action of hormones. Cyclic AMP seems to function as an ' intracellular second messenger' mediating the action of many different hormones (Sutherland, 0ye & Butcher, 1965; Sutherland & Robison, 1966; Robison, Butcher & Sutherland, 1968). The primary hormonal message arriving at a cell is translated into a secondary message, represented by an increase in the intracellular level of cyclic AMP, which is then responsible for influencing the effector system. Some of the most compelling evidence for this hypothesis is that exogenous cyclic AMP has the same effect as certain hormones (Haynes, Koritz & Peron, 1959; Orloff & Handler, 1962; Bitensky & Burstein, 1965; Grantham & Burg, 1966; Novales & Davis, 1967). Cellular activity therefore appears to be regulated by the intracellular level of cyclic AMP. The concentration of cyclic AMP in cells is determined by the balance which exists between the two competing processes of synthesis and degradation. Cyclic AMP is synthesized from ATP by an enzyme adenyl cyclase which is associated with the plasma membrane (Sutherland, Rail & Menon, 1962; Davoren, & Sutherland, 1963). The concept has developed that many hormones act by stimulating adenyl cyclase to synthesize cyclic AMP. The adenyl cyclase in membrane fractions of certain tissues will respond to hormones and competitors in the same way as the intact cells (Murad et al. 1962; Bar & Hechter, 1969). Another line of evidence is that an increase in cyclic AMP level coincides with or, in some cases, precedes the observed action of many different hormones (Butcher, et al. 1965; Handler et al. 1965; Robison et al. 1965; Abe et al. 1969). When the hormonal stimulus is withdrawn, the cyclic AMP concentration is reduced to its unstimulated level by means of a specific phosphodiesterase which converts cyclic AMP to adenosine 5'-monophosphate (5'-AMP). In an unstimulated cell the phosphodiesterase dominates resulting in a low level of cyclic AMP; in a stimulated cell, however, the enhanced adenyl cyclase activity can overcome the