Novel effects of propranolol -: Release of internal Ca2+ followed by activation of capacitative Ca2+ entry in Madin Darby canine kidney cells

The effect of propranolol on Ca2+ signalling in Madin Darby canine kidney (MDCK) cells was investigated by using fura-2 as a Ca2+ probe. Propranolol increased cytosolic free Ca2+ levels ([Ca2+](i)) in a concentration-dependent manner between 0.1 and 1 mM. The response was partly inhibited by external Ca2+ removal. In Ca2+-free medium pretreatment with 0.2 mM propranolol partly inhibited the [Ca2+](i) rise induced by 1 mu M thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+ pump; but pretreat ment with thapsigargin abolished propranolol-induced Ca2+ release. Addition of 3 mM Ca2+ induced a [Ca2+](i) rise after pretreatment with 0.2 mM propranolol in Ca2+-free medium. Propranolol (0.2 mM) inhibited 25% of thapsigargin-induced capacitative Ca2+ entry. Suppression of 1,4,5-trisphosphate (IP3) formation by 2 mu M U73122, a phospholipase C inhibitor, did not alter 0.2 mM propranolol-induced internal Ca2+ release. Propranolol (1 mM) also increased [Ca2+](i) in human neutrophils. Collectively, we have found that 0.2 mM propranolol increased [Ca2+](i) in MDCK cells by releasing Ca2+ from thapsigargin-sensitive Ca2+ stores in an IP3-independent manner, followed by Ca2+ influx from external space. Independently, propranolol was able to inhibit thapsigargin-induced capacitative Ca2+ entry. (C) 2000 Elsevier Science Inc. All rights reserved.