AJP - Heart and Circulatory Physiology, Vol 261, Issue 6 1848-H1854, Copyright © 1991 by American Physiological Society

ARTICLES

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

D. J. Cushing, S. R. Makujina, M. H. Sabouni and S. J. Mustafa
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina 27858-4354.

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.

This article has been cited by other articles:

				N. Harada, S. Sakamoto, Y. Niwa, and Y. Nakaya Involvement of adenosine in vascular contractile preconditioning Am J Physiol Heart Circ Physiol, June 1, 2001; 280(6): H2911 - H2919. [Abstract] [Full Text] [PDF]

				W. Abebe and S. J. Mustafa A1 adenosine receptor-mediated Ins(1,4,5)P3 generation in allergic rabbit airway smooth muscle Am J Physiol Lung Cell Mol Physiol, November 1, 1998; 275(5): L990 - L997. [Abstract] [Full Text] [PDF]