Stimulatory effects of vasoactive intestinal peptide and pituitary adenylate cyclase-activating peptide on tuberoinfundibular dopaminergic neuron activity in estrogen-treated ovariectomized rats and their correlation with prolactin secretion.

摘要

The effects of central administration of vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) on hypothalamic tuberoinfundibular dopaminergic neuron activity and serum prolactin (PRL) levels were reported. Adult female Sprague-Dawley rats overiectomized for 2 weeks, implanted with subcutaneous estrogen-containing capsules and intracerebroventricular (i.c.v.) cannulae for 6 days were used for experiments. I.c.v. injections of VIP or PACAP were performed in conscious rats in the morning, and the injected rats were decapitated at various times afterwards. Serum sample and the median eminence tissue were collected from each rat. The levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 3,4-dihydroxyphenylalanine (DOPA) in the median eminence were determined by high-performance liquid chromatography with electrochemical detection. Serum PRL levels were determined by radioimmunoassay. I.c.v. administration of VIP (1 microgram/3 microliter) significantly increased median eminence DOPAC/DA ratio at 30 min, and serum PRL level at 15 min. The same dose of VIP (1 microgram), but not higher (10 micrograms) or lower (0.1 microgram), was also effective in stimulating the median eminence DOPA accumulation 35 min after the injection. The effect of VIP (1 microgram) on median eminence DOPA could be blocked by coadministration of a VIP antagonist, VIP6-28 in 10- and 30-, but not in 1- or 0.1-microgram doses. On the other hand, i.c.v. administration of PACAP (10 micrograms) stimulated median eminence DOPAC and lowered serum PRL levels at 30 min. All doses of PACAP used (0.1, 1 and 10 micrograms/ rat, i.c.v.) significantly increased median eminence DOPA concentrations at 60 min. The stimulatory effect of PACAP (0.1 microgram) on median eminence DOPA could also be blocked by coadministration of a PACAP antagonist, PACAP6-38 (in 10 to 100 x higher doses). In summary, central administration of either VIP or PACAP exhibited a stimulating effect on TIDA neuron activity through specific receptors. Serum PRL levels, however, were stimulated and inhibited by VIP and PACAP, respectively.