DELTA(9)-TETRAHYDROCANNABINOL ACTIVATES [CA2+], INCREASES PARTLY SENSITIVE TO CAPACITATIVE STORE REFILLING

Delta(9)-Tetrahydrocannabinol induces [Ca2+](i) increases in DDT1MF-2 smooth muscle cells. Both Ca2+ entry and release from intracellular Ca 2+ stores were concentration dependently activated. The Ca2+ entry com ponent contributed most to the increases in [Ca2+](i). Stimulation wit h Delta(9)-tetrahydrocannabinol after functional downregulation of int racellular Ca2+ stores by longterm thapsigargin treatment, still induc ed a major Ca2+ entry and a minor Ca2+ release component. Thapsigargin sensitive influx and release were selectively inhibited by the cannab inoid CB1 receptor antagonist SR141716A. No effects on [Ca2+](i) were obtained after stimulation with the CB2 receptor agonist palmitoyletha nolamide. This study is the first demonstration of (1) Ca2+ release fr om thapsigargin sensitive intracellular stores and capacitative Ca2+ e ntry via CB1 receptor stimulation and of (2) an additional Delta(9)-te trahydrocannabinol induced thapsigargin insensitive component, mainly representing Ca2+ influx which is neither mediated by CB1 nor CB2 rece ptor stimulation. (C) 1997 Elsevier Science B.V.