MESSENGER-RNA FOR THE GUANINE-NUCLEOTIDE-BINDING REGULATORY PROTEIN (G-PROTEIN) IS REDUCED IN THE ACUTE ISCHEMIC MYOCARDIUM

It has been reported that the function of the guanine-binding regulato ry protein (G protein), especially the a subunit of the stimulatory G protein (Gs alpha), in myocardium is decreased with acute ischemia, Ho wever, it is unclear whether this decrease is due to transcriptional o r post-transcriptional changes. Moreover, no studies have examined the distribution of G protein mRNA in ischemic myocardium using in situ h ybridization. The purpose of this study was to explore alterations in mRNA of G proteins (Gs and Gi) in ischemic hearts using in situ hybrid ization. We measured the levels of mRNA for Gs alpha and Gi alpha in i schemic and non-ischemic myocardium by in situ hybridization using a r adioisotope imaging system. We compare these mRNA levels in ischemic a nd non-ischemic myocardium with Northern blot analysis and the protein levels of G proteins by Western blot analysis. The mRNA for Gs alpha and Gi alpha was distributed diffusely in normal hearts, Levels of mRN A detected by in situ hybridization were substantially reduced by acut e ischemia, and these results were confirmed by Northern and Western b lot analysis. These results suggest that decreased levels of mRNA and protein for G proteins may underlie the impaired function of the recep tor-G protein-adenylate cyclase system in ischemic myocardium. In addi tion, quantitative evaluation of mRNA is possible by in situ hybridiza tion and correlates well with Northern analysis.