IMMUNOCYTOCHEMICAL STUDIES OF THE G(I) PROTEIN-MEDIATED MUSCARINIC RECEPTOR ADENYLYL-CYCLASE SYSTEM

The localization of three key signal transduction components was indic ated in rat heart tissue by immunocytochemical and histochemical exper iment. It was shown that: 1. The M2 muscarinic receptors are localized along outer cell membranes and T-tubule membranes of cardiomyocytes b ut additionally at membranes of endothelial cells and fibroblasts. 2. G(i alpha) was found along outer cell membranes of cardiomyocytes and other cells of the heart and also inside the cells of the perinuclear space in close contact to the nuclei envelope and the endoplasmic reti culum membranes. G(o alpha) were found to be associated mainly in atri al tissue, especially at the nerval (neuronal) endings located among t he cardiac muscle cells. This was shown in parallel incubation with sp ecific neuronal antibody as a marker for these structures. 3. Adenylyl cyclase was localized along the sarcolemma and the T-tubule membranes in normal cardiomyocytes of rat and guinea pig hearts. Under ischemic conditions, the adenylyl cyclase was also seen in junctional sarcopla smic reticulum membranes. The reasons for this changed localization ne ed further elucidation. Binding of the adenylyl cyclase within the mol ecular structure of the membrane or variation of the marker penetratio n remain to be clarified.