Newly synthesized protein secretion in rat lacrimal gland: post-second messenger synergism

The vasoactive intestinal peptide (VIP) induces a concentration-dependent secretion of newly synthesized (3H labeled) proteins from lacrimal gland fragments. Maximal secretory response is approximately 20% of total labeled proteins secreted for a 40-min stimulation and half-maximal secretory response is obtained at 3.8 +/- 0.2 nM VIP. The cholinergic (muscarinic) and VIPergic stimulations synergistically interact in eliciting newly synthesized protein secretion. Carbachol (0.3 microM) and the phorbol ester PMA (1 microM) potentiate the secretory response to VIP (10 nM), forskolin (3 microM), and dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) (0.5 mM) both in the absence and presence of 2.5 mM extracellular calcium. The calcium ionophore A23187 (1 microM) potentiates the cAMP-dependent responses only in the presence of extracellular calcium. We propose that newly synthesized protein secretion from rat lacrimal glands is controlled by two systems interacting synergistically at a step distal to the production of intracellular second messengers. The potentiating effect of agonists acting through the calcium-dependent pathway on the cAMP-dependent secretory response may involve both calcium and diacylglycerol.