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 μM thapsigargin, an inhibitor of the endoplasmic reticulum Ca²⁺ pump; but pretreatment 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 μM 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. Copyright (C) 2000 Elsevier Science Inc.