Pharmacology of noradrenergic-mediated changes in pineal gland N-acetyltransferase activity in adult and developing rats

Using in vitro pineal gland organ culture technique the present set of experiments were conducted to: (1) characterize the approximate time during development when noradrenergic presynaptic, and postsynaptic adrenoceptor-coupled cyclic AMP mechanisms controlling pineal gland NAT activity reach adult-like status; and (2) to determine the degree to which alpha-1-adrenoceptor activation contributes to the induction of NAT activity during development.; A comparison of pineal gland NAT activity in adult and gestational 19 day old animals revealed that adult pineal glands were responsive to presynaptic, beta-adrenoceptor, or cyclic AMP-enhancing drugs while gestational 19 day-old fetal pineal gland NAT activity was slightly elevated in response to treatment by each of the adrenoceptor or intracellular acting drugs but unaffected by treatment with presynaptic acting drugs. It was concluded that pineal glands of 19 gestational day old fetal animals lack functional presynaptic neural control mechanisms but do possess beta-adrenoceptor and second messenger NAT control mechanisms. Administration of presynaptic acting drugs in vitro to pineal glands removed from 19, 20, and 21 gestational day old and newborn animals revealed that presynaptic mechanisms developed differentially over the last 3 days of gestation and by the day of birth each of the presynaptic mechanisms of synthesis, storage, release, reuptake, and catabolism appeared to be functional.; To determine when noradrenergic mechanisms reach adult-like status, NAT activity was measured in pineal glands from neonatal, adolescent and adult animals following in vitro treatment with the same pharmacological agents used in the previous experiments. Basal levels of NAT activity increased from birth until 10 days of age and then returned to adult-like levels by 25 days of age. NAT activity was maximally stimulated by presynaptic or postsynaptic acting drugs between 5 and 10 days of age and reached adult-like levels by postnatal day 25.; Alpha-1-adrenoceptor-mediated changes in pineal gland NAT activity were assessed in adult and developing animals. Adult pineal gland NAT activity was stimulated by relatively high doses of phenylephrine and blocked by either propranolol or prazosin indicating that phenylephrine acts as a weak beta-adrenoceptor agonist as well as an alpha-1-adrenoceptor agonist. Combined phenylephrine and isoproterenol treatment caused a synergistic increase in pineal gland NAT activity in adult animals. Prazosin attenuated basal NAT activity between the gestational day 21 and postnatal day 10. Prazosin-reversible phenylephrine-induced increases in NAT activity were observed at ages between gestational day 19 and 50 days of age, demonstrating that pineal gland alpha-1-adrenoceptors are functional early in development. Alpha-1-adrenoceptor mediated changes in pineal gland NAT activity reach adult-like levels by 25 days of age.