We have compared the formation of pores in rat submandibular acinar cells in response to 2′, 3′-O-(4-benzoylbenzoyl) adenosine 5′-triphosphate (Bz-ATP) and maitotoxin. Bz-ATP (100 μM) permeabilized the cells to ethidium bromide. The uptake of ethidium increased to 29±1% of maximal uptake in 10 min. dl-Propranolol (300 μM) inhibited the Bz-ATP-induced uptake of ethidium bromide by 40% without affecting the P2X 7-gated cation channel. The inhibitory effect of dl-propranolol on the formation of pores by Bz-ATP was reproduced by d-propranolol, an optical isomer with very poor β-blocking activity. Tenidap, an antiinflammatory drug, enhanced the permeabilization in response to Bz-ATP. Propanolol inhibited the response to tenidap plus Bz-ATP. The effect of propranolol was reproduced by labetolol, a β-adrenergic antagonist with membrane-stabilizing properties, but not by …