Cytosolic heparin inhibits muscarinic and alpha-adrenergic Ca2+ release in smooth muscle. Physiological role of inositol 1,4,5-trisphosphate in pharmacomechanical coupling.

摘要: Abstract In order to test the physiological significance of inositol 1,4,5-trisphosphate (InsP3) in pharmacomechanical coupling, we have utilized two near-physiological systems, which relatively high molecular weight solutes can be applied intracellularly and receptor coupling is retained: beta-escin permeabilization reversible permeabilization. We showed that smooth muscle permeabilized with beta-escin, one saponin esters, alpha 1-adrenergic (phenylephrine) muscarinic (carbachol) agonists, as well caffeine InsP3, cause contractions mediated by Ca2+ release. These were calmodulin-dependent blocked depletion stored sarcoplasmic reticulum. Intracellular heparin (Mr = about 5000), a blocker InsP3 binding its specific inhibitor InsP3-induced release muscles, inhibited responses agonists but not those caffeine, nor did it block enhanced contractile response cytoplasmic induced GTP gamma S. Neomycin carbachol, caffeine. reversibly ileum cells, loaded Fura-2 acid heparin, intracellular carbachol Ca2+-free, K+ solution. Heparin inhibit (with 1.2 mM Ca2+) had no significant inhibitory effects on carbachol-induced presence extracellular Ca2+. results, obtained under conditions, support conclusion major messenger component components influx or potentiation