A Ca²⁺-linked increase in coupled cAMP synthesis and hydrolysis is an early event in cholinergic and β-adrenergic stimulation of parotid secretion

The dynamics and compartmental characteristics of cAMP metabolism were examined by ¹⁸O labeling of cellular adenine nucleotide α phosphoryls in rat parotid gland stimulated to secrete with β-adrenergic and cholinergic agents. The secretory response occurred in association with a rapidly increased rate of cAMP hydrolysis apparently coordinated with an equivalent increase in the rate of cAMP synthesis, since the cellular concentration of cAMP remained unchanged. The magnitude of this metabolic response was equivalent to the metabolism of 10-75 times the cellular content of cAMP within the first minute of stimulation. This increased metabolic rate occurred only during the early (1-3 min) period of stimulation, in what appeared to be an exclusive cellular compartment distinguished by a unique distribution of ¹⁸O among adenine nucleotide α phosphoryls. This ¹⁸O distribution contrasted with that produced by forskolin, which increased cellular cAMP concentration and elicited only a delayed response missing the early secretory component. The early acceleration of cAMP metabolism appeared linked to a stimulus-induced increase in intracellular Ca²⁺ concentration, since the Ca²⁺ ionophore ionomycin produced the same metabolic response in association with secretion. These observations suggest that cAMP metabolism is involved in stimulus-secretion coupling by a Ca²⁺-linked mechanism different from that in which cAMP plays the role of a second messenger.