PT - JOURNAL ARTICLE AU - F Zorzato AU - E Scutari AU - V Tegazzin AU - E Clementi AU - S Treves TI - Chlorocresol: an activator of ryanodine receptor-mediated Ca2+ release. DP - 1993 Dec 01 TA - Molecular Pharmacology PG - 1192--1201 VI - 44 IP - 6 4099 - http://molpharm.aspetjournals.org/content/44/6/1192.short 4100 - http://molpharm.aspetjournals.org/content/44/6/1192.full SO - Mol Pharmacol1993 Dec 01; 44 AB - In the present study we investigated the effect of the compound chlorocresol on intracellular Ca2+ homeostasis. Three different systems that have been shown to express the ryanodine receptor Ca2+ channel were chosen, i.e., skeletal muscle sarcoplasmic reticulum, cerebellar microsomes, and PC12 cells. In skeletal muscle sarcoplasmic reticulum, 4-chloro-m-cresol was found to be a potent activator of Ca2+ release mediated by a ruthenium red/caffeine-sensitive Ca2+ release channel. In cerebellar microsomes, this compound released Ca2+ from an inositol-1,4,5-trisphosphate-insensitive store, suggesting that there too it was acting at the ryanodine receptor level. When tested on PC12 cells, chlorocresol released Ca2+ from a caffeine- and thapsigargin-sensitive intracellular store. In addition, the compound was capable of releasing Ca2+ after pretreatment of PC12 cells with bradykinin, suggesting that it acts on a channel contained within an intracellular Ca2+ store that is distinct from that sensitive to inositol-1,4,5-trisphosphate. Structure-activity relationship analyses suggest that the chloro and methyl groups in chlorocresols are important for the activation of the ryanodine receptor Ca2+ release channel.