Opiates inhibit ion conductances elicited by cell swelling and cAMP in cultured cells

Abstract

The effect of several opiate compounds on I- efflux was investigated in cultured cell lines. I- efflux was evoked by two distinct stimuli, namely cell swelling and elevation of cellular cAMP levels by prostaglandin E2. Cells expressing the multidrug resistance P-glycoprotein were found to have increased I- efflux in response to hypo-osmotic challenge. This increased I- efflux in P-glycoprotein containing cells was reduced to levels found in parental cells by the opiates morphine, pentazocine and naloxone. Addition of prostaglandin E2 to T84 cells resulted in elevated cellular cAMP levels and a significant I- efflux. This cAMP stimulated efflux was also inhibited by several opiates. None of the opiates was able to alter cAMP levels or protein kinase A mediated phosphorylation of immunoprecipitated cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel in T84 cells. The ability of opiates to alter ion conductances is discussed in relation to the anti-diarrheal effects of these compounds. Show more