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 and adenosine receptor-mediated relaxation. Ring segments of coronary artery were suspended in organ baths for measurement of isometric force. PDB (10 nM-1-mu-M) 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-mu-M). Treatment of rings with either adenosine, CAD, or NECA (100-mu-M) significantly attenuated the PDB-induced contraction, whereas treatment with either sodium nitroprusside (SNP: 1-mu-M) or isoproterenol (Isop; 1-mu-M) 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-mu-M). 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.