SEE-SAW SIGNAL-PROCESSING - RECIPROCAL EFFECTS OF STIMULUS DEPRIVATION ON VASOACTIVE INTESTINAL PEPTIDE-STIMULATED ADENOSINE-3',5'-MONOPHOSPHATE AND GUANOSINE 3',5'-MONOPHOSPHATE ACCUMULATION IN RAT PINEALOCYTES

In the present study the effects of stimulus deprivation on vasoactive intestinal peptide (VIP)- and alpha-1-adrenergically mediated amplification of VIP-stimulated cAMP and cGMP accumulation were examined. Dispersed pinealocytes were prepared from either Sprague-Dawley rats maintained for 2 weeks in a normal lighting schedule providing 14 h of light/day (LD cells) or from animals maintained in constant lighting (LL cells). LL treatment enhanced the VIP-stimulated cGMP by 70%. In LL cells, phenylephrine potentiated the VIP-stimulated cAMP response, but did not potentiate the VIP-stimulated cGMP response. Potentiation of the cAMP response to VIP can be produced in LD cells by treatment with agents that elevate intracellular Ca2+ (depolarizing concentrations of K+ or A23187) or an activator of protein kinase-C [4-beta-phorbol 12-myristate 13-acetate (PMA)]. LL treatment abolished the potentiating effects of K+ or A23187 on cAMP and cGMP responses in VIP-treated cells. In contrast, LL treatment augmented the PMA potentiation of VIP-stimulated cAMP response. The potentiation effects of PMA and K+ on the cGMP response in VIP-treated cells, however, were suppressed by LL treatment. To further investigate the involvement of postreceptor mechanisms, forskolin was used to stimulate pineal cAMP and cGMP accumulation. LL treatment had similar effects on the forskolin-stimulated cyclic nucleotide responses, with one exception. Depolarizing concentrations of K+ potentiated the forskolin-stimulated cAMP response while having no effect on the VIP-stimulated cAMP response. These findings suggest that LL treatment results in a larger VIP-stimulated cAMP responses, while its effect on the cGMP response is inhibitory. LL treatment appears to inhibit a step distal to elevation of intracellular Ca2+ which is of importance to the alpha-1-adrenergic potentiation of VIP-stimulated cAMP and cGMP responses.