BACKGROUND: Norepinephrine is the main neurotransmitter controlling melatonin secretion in the mammalian pineal gland. Presynaptic autoregulation of norepinephrine release from the sympathetic nerve fibers in the pineal gland is poorly known.
METHODS: Uptake and depolarization-evoked release of (3)H-norepinephrine were investigated in vitro using pieces of the pig pineals. Specific antagonists and agonists of alpha(2)-adrenoceptors were employed for the characterization of alpha(2)-adrenoceptors involved in the autoregulation of depolarization-evoked release of norepinephrine in the pig pineal.
RESULTS: The level of neuronal uptake of norepinephrine in the pig pineal was 3.5+/-0.9 pmol/h/mg of wet tissue and represented about 77% of the total tissue radioactivity. Potassium ions at concentration of 60 mM significantly evoked tritium release. This effect was abolished in the absence of extracellular Ca(2+) and was diminished in the presence of Cd(2+). Antagonists of alpha(2)-adrenoceptors increased depolarization evoked tritium release. The order of its potency (based on pED(30)) was rauwolscine > phentolamine > BRL 44408 > WB 4101> RS 79948 = yohimbine > prazosin > imiloxan. alpha(2)-agonists decreased K(+) evoked release of tritium with the order of potency: UK14,304 > norepinephrine = guanfacine > oxymetazoline.
CONCLUSION: The processes of neuronal uptake and depolarization-evoked release of norepinephrine from the sympathetic nerve endings in the pig pineal gland have been demonstrated. The studies with the use of adrenergic antagonists and agonists indicate that the sympathetic nerve fibers in the pig pineal gland possess functional presynaptic alpha(2)-adrenoceptors, which are involved in norepinephrine release inhibition. Due to the pharmacological properties these receptors closely resemble the subtype alpha(2A).