OPIATES INHIBIT ION CONDUCTANCES ELICITED BY CELL SWELLING AND CAMP IN CULTURED-CELLS

The effect of several opiate compounds on I- efflux was investigated i n cultured cell lines. I- efflux was evoked by two distinct stimuli, n amely cell swelling and elevation of cellular cAMP levels by prostagla ndin E(2). Cells expressing the multidrug resistance P-glycoprotein we re found to have increased I- efflux in response to hypo-osmotic chall enge. This increased I- efflux in P-glycoprotein containing cells was reduced to levels found in parental cells by the opiates morphine, pen tazocine and naloxone. Addition of prostaglandin E(2) to T84 cells res ulted in elevated cellular cAMP levels and a significant I- efflux. Th is cAMP stimulated efflux was also inhibited by several opiates. None of the opiates was able to alter cAMP levels or protein kinase A media ted phosphorylation of immunoprecipitated cystic fibrosis transmembran e conductance regulator (CFTR) Cl- channel in T84 cells. The ability o f opiates to alter ion conductances is discussed in relation to the an ti-diarrheal effects of these compounds.