Functional Antagonism between Hormone Receptor Systems: Modulation of Glycoprotein Secretion in Secretory Epithelial Cells

A physiologic response such as mucin secretion from epithelial cells in vivo may be under the control of several endogenous substances such as acetylcholine, norepinephrine, and vasoactive intestinal peptide (VIP). These substances may simultaneously activate distinct membrane receptors that exist on the same epithelial cells, and this activation may result in reciprocal physiologic responses or functional antagonism. To test whether simultaneous activation of the VIP and muscarinic receptors or of β-adrenoreceptors and muscarinic receptors affect mucin secretion in a reciprocal manner, we studied some characteristics of the resultant physiologic response in human epithelial cells secreting radiolabeled mucin-like glycoprotein (MLGP). Both basal and methacholine (M.chol)-induced MLGP secretion could be blocked by VIP (1 pM to 1 µM) and by isoproterenol (ISO) (0.1 nM to 10 nM) in a concentration-dependent and reversible manner. In a membrane preparation from the same cells, VIP (1 to 1,000 nM) and ISO (0.1...