Because very little is known regarding the control of enzyme secretion in developing parotid glands, the effects of various secretagogues on cyclic AMP levels and amylase release were studied in rats at various times after birth. In parotid fragments or slices incubated with isoproterenol or epinephrine (40 μM) in vitro, neither cyclic AMP elevation nor amylase release was achieved at 8 days postnatally. In in vivo studies, secretion of amylase at this age was also refractory to stimulation with these hormones or carbamylcholine. In animals older than 15 days, highly significant rise in cyclic AMP content occurred 5 min after exposure of the glands to the catecholamines in vitro, and the magnitude of this elevation was incremental with age. Thus, in 15-day-old animals adrenergic stimulation produced a 2-fold rise in cyclic AMP levels (from 9.3 ± 1.0 pmol/mg protein to 20.9 ± 4.7, mean ± SE); at 25 days the increase was 7–8 times the basal value (from 2.7 ± 0.3 to 21.3 ± 3.9); and at 8 weeks the rise was 8-fold with epinephrine (from 3.2 ± 0.3 to 24.4 ± 7.5) and 12-fold after isoproterenol (from 3.2 ± 0.3 to 39.2 ± 9.2). At these ages, adrenergic stimulation led to a 2− to 3-fold increase in amylase secretion compared to unstimulated control levels. When isoproterenol (16 μg/g body weight) was injected intraperitoneally in intact animals 15 days of age or older cyclic AMP levels 5 min later were increased 2–3 times in 15− and 25-day-old animals (from 13.9 ± 4.4 to 49.3 ± 3.9 and 31.3 ± 4.0, respectively) and >100-fold in mature animals (1211 ± 437). Greater than 40% of the stored amylase was released from the glands in 30 min, a quantity comparable to that found in vitro. The data demonstrate that the responsiveness of the parotid gland to catecholamines is age dependent, and that development of secretory function precedes full morphologic and biochemical development.SpeculationThe identification of a stage in exocrine development when the immature parotid glands are refractory to secretory stimuli represents an important model for the study of stimulus-secretion coupling. The acquisition of mature secretory function may depend upon the relationship between the number of cell surface hormone receptors and acinar maturation.