Differential effects of FK506 and cyclosporin A on catecholamine release from bovine adrenal chromaffin cells.
1 The effects of the immunosuppressants, tacrolimus (FK506) and cyclosporin A (CsA), on catecholamine (CA) release were examined in cultured bovine adrenal chromaffin cells. 2 In intact cells, FK506 (1-30 microM) inhibited CA release stimulated by acetylcholine (ACh; 100 microM), 1,1-dimethyl-4-phenyl-piperazinium (DMPP, 10 microM) or high K+ (40 mM). CsA (1-30 microM) had a little inhibitory effect on the ACh- or DMPP-stimulated CA release, whereas it enhanced the high K(+)-stimulated CA release. 3 In beta-escin-permeabilized cells, FK506 inhibited CA release stimulated by Ca2+ (1 and 10 microM) in the presence and absence of MgATP (2 mM). CsA induced CA release under Ca(2+)-free condition and enhanced the Ca(2+)-stimulated CA release in the presence and absence of MgATP. 4 It is known that the Ca(2+)-dependent exocytosis involves at least two distinct steps, ATP-requiring priming stage and ATP-independent fusion step in adrenal chromaffin cells. Therefore, it is suggested that FK506 inhibits the Ca(2+)-dependent exocytosis probably at the fusion step whereas CsA induces CA release from bovine adrenal chromaffin cells.
Matsumura
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Department of Pharmacology, The Nippon Dental University School of Dentistry at Niigata, Hamaura-cho, Niigata 951-8580, Japan.
Kuwashima
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Kimura
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology*; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004928:Escin / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D018722:Nicotinic Agonists / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011722:Pyrethrins / Q000494:pharmacology; D016559:Tacrolimus / Q000494:pharmacology*
D002395:Catecholamines; D007166:Immunosuppressive Agents; D018722:Nicotinic Agonists; D011722:Pyrethrins; C017160:cypermethrin; D004246:Dimethylphenylpiperazinium Iodide; D004928:Escin; D016572:Cyclosporine; D000109:Acetylcholine; D011188:Potassium; D016559:Tacrolimus