Protein kinase C and phospholipase C in adenosine receptor-mediated relaxation in coronary artery.
The effect of adenosine, 2-chloroadenosine (CAD), and 5'-(N-ethylcarboxamido)-adenosine (NECA) on the contraction produced by phorbol 12,13-dibutyrate (PDB) was investigated in porcine coronary artery in vitro to determine whether adenosine receptor-mediated relaxation was linked to protein kinase C. Also, the coronary relaxation produced by adenosine and NECA in KCl-contracted coronary rings was investigated before and after treatment with the phospholipase C inhibitor neomycin to examine a possible link between phospholipase C and adenosine receptor-mediated relaxation. Ring segments of coronary artery were suspended in organ baths for measurement of isometric force. PDB (10 nM-1 microM) caused concentration-dependent contraction, and this response was significantly attenuated by pretreatment with the protein kinase C inhibitor staurosporine (200 nM) but not 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine (10 microM). Treatment of rings with either adenosine, CAD, or NECA (100 microM) significantly attenuated the PDB-induced contraction, whereas treatment with either sodium nitroprusside (SNP; 1 microM) or isoproterenol (Isop; 1 microM) did not affect the contraction produced by PDB. The attenuation of the PDB-induced contraction by adenosine and its analogues was blocked by prior treatment of the coronary rings with 8-phenyltheophylline (10 microM). In a separate series of experiments, pretreatment of rings with the phospholipase C inhibitor neomycin (1 mM) resulted in a significant attenuation of the relaxing response to both adenosine and NECA while having no significant effect on the relaxation-response to SNP or Isop. These results provide indirect evidence that adenosine receptor-mediated relaxation in porcine coronary artery may be linked to modulation of protein kinase C and phospholipase C.
Cushing
D J
DJ
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina 27858-4354.
Makujina
S R
SR
Sabouni
M H
MH
Mustafa
S J
SJ
D015762:2-Chloroadenosine / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D011983:Receptors, Purinergic / Q000502:physiology*; D019311:Staurosporine; D013552:Swine; D010738:Type C Phospholipases / Q000378:metabolism*
D000470:Alkaloids; D011983:Receptors, Purinergic; D015762:2-Chloroadenosine; D009599:Nitroprusside; D019830:Adenosine-5'-(N-ethylcarboxamide); D015240:Phorbol 12,13-Dibutyrate; D011189:Potassium Chloride; D011493:Protein Kinase C; D010738:Type C Phospholipases; D019311:Staurosporine; D000241:Adenosine; D007545:Isoproterenol