1750539

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6 Pt 2

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.

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0002-9513

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H1848-54

pubmed-meshheading:1750539-2-Chloroadenosine, pubmed-meshheading:1750539-Adenosine, pubmed-meshheading:1750539-Adenosine-5'-(N-ethylcarboxamide), pubmed-meshheading:1750539-Alkaloids, pubmed-meshheading:1750539-Animals, pubmed-meshheading:1750539-Coronary Vessels, pubmed-meshheading:1750539-Isoproterenol, pubmed-meshheading:1750539-Muscle, Smooth, Vascular, pubmed-meshheading:1750539-Muscle Contraction, pubmed-meshheading:1750539-Muscle Relaxation, pubmed-meshheading:1750539-Nitroprusside, pubmed-meshheading:1750539-Phorbol 12,13-Dibutyrate, pubmed-meshheading:1750539-Potassium Chloride, pubmed-meshheading:1750539-Protein Kinase C, pubmed-meshheading:1750539-Receptors, Purinergic, pubmed-meshheading:1750539-Staurosporine, pubmed-meshheading:1750539-Swine, pubmed-meshheading:1750539-Type C Phospholipases

Protein kinase C and phospholipase C in adenosine receptor-mediated relaxation in coronary artery.

Journal Article, Research Support, U.S. Gov't, P.H.S.