VASOPRESSIN POTENTIATION OF THE MELATONIN SYNTHETIC PATHWAY VIA SPECIFIC V-1A RECEPTORS IN THE RAT PINEAL-GLAND

The pineal gland releases the 'time-keeping' hormone melatonin followi ng a rhythmic sympathetic input which translates light information. Th e aim of this work was to study the role and mechanisms of action of t he central vasopressinergic input on pineal cAMP-dependent melatonin s ynthesis in the rat. The pineal was found to display vasopressin recep tors of the V-1a subtype, as the V-1a antagonist [I-125]HO-LVA bound i n a saturable manner to pineal membranes with a high affinity (k(d) = 10 pM) and a maximal binding capacity (B-max) of 13 fmol/mg protein. V asopressin was able to displace [I-125]HO-LVA binding in a dose-depend ent manner (k(i) = 1.9 nM). Vasopressin had no effect on the basal cAM P level and melatonin secretion in cultured rat pinealocytes. However, it clearly and dose-dependently (EC(50) = 7 nM) potentiated by 2-3 ti mes cAMP accumulation and by 1.5-2.5 times melatonin secretion induced by moderate noradrenergic stimulation. On strongly stimulated pinealo cytes, however, vasopressin could potentiate cAMP accumulation, but no t melatonin secretion. The potentiatory effect of vasopressin was inhi bited in the presence of the V,, antagonist. These results indicate th at vasopressin is a potent modulator of rat pineal synthetic activity.