Peptidergic stimulation and inhibition of lacrimal gland adenylate cyclase

Vasoactive intestinal peptide (VIP) and d-ala2-methionine enkephalinamide (DALA, a long-lasting enkephalin analogue) were used to investigate the peptidergic control of lacrimal gland function. To characterize the mechanism by which VIP stimulates and DALA inhibits lacrimal peroxidase secretion, the effect of these peptides on adenylate cyclase was measured. In addition, enzyme activity was measured in the presence of forskolin alone or in combination with DALA. VIP stimulated adenylate cyclase in a time- and dose-dependent manner. Negative control of adenylate cyclase was shown with the addition of DALA to membrane preparations. The enkephalin analogue inhibited basal activity approximately 65% at the maximum dose tested. The percent inhibition of VIP-stimulated activity by DALA was similar to the inhibition of basal activity. To determine if the inhibition of stimulated activity occurred at level of the VIP receptor, the effect of DALA on the response to forskolin was measured. Forskolin-stimulated adenylate cyclase activity was significantly reduced to approximately 50% in the presence of DALA. We conclude that lacrimal gland adenylate cyclase is subject to peptidergic regulation involving both stimulatory and inhibitory receptor-mediated controls.