Ovine pineal alpha 1-adrenoceptors: characterization and evidence for a functional role in the regulation of serum melatonin.

Plasma melatonin in sheep increases to nocturnal levels rapidly (10-20 min) after dark onset. This increase is blocked by iv prazosin (1 mg), but not propranolol (6 mg). Prazosin also blocks the elevation in pineal melatonin content after dark onset, but does not significantly alter the rise in N-acetyltransferase activity or the elevation in pineal N-acetylserotonin content. Since the nocturnal elevation in N-acetyltransferase, a neurally regulated event, was unaltered, this suggests that prazosin does not significantly impair the transmission of neural signals from the eye to the gland, but does act on pineal alpha 1-adrenoceptors to block melatonin production. This is supported by binding studies in ovine pineal membranes using [125I] iodo-2-[beta-(4-hydroxyphenyl)ethylaminomethyl]tetralone, which revealed that binding is rapid, reversible, saturable, and stereo-specific. Saturation studies indicated the presence of a single class of binding sites, with an equilibrium binding constant (Kd) of 32 +/- 6 pM and a maximum binding of 139 +/- 19 fmol/mg protein. The relative potencies of several adrenergic agonists and antagonists in competition studies indicated that the receptor belongs to the alpha 1-subclass of adrenoceptors. Together, these data suggest that melatonin synthesis in the sheep pineal gland is controlled in part by an alpha 1-adrenoceptor mechanism at a step beyond N-acetylation.