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

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.