Regional localization and abundance of calcitonin gene-related peptide receptors in guinea pig heart

Calcitonin gene-related peptide (CGRP) is a neurotransmitter that is released within the heart during myocardial ischemia, The present study was done to determine the regional localization and abundance of CGRP receptors in the guinea pig heart. CGRP binding sites in 20 mum frozen sections of heart were labeled using [I-125]CGRP. Non-specific binding was determined in the presence of 1 muM unlabeled CGRP or CGRP(8-37). Significant amounts of specific CGRP binding were identified in atrial and ventricular myocardium, all portions of the conducting system, coronary arteries, the aorta and pulmonary trunk and intracardiac ganglia, Specific binding of CGRP to the left atrium was two-fold higher than binding to the right atrium (0.667 +/- 0.052 v 0.340 +/- 0.029 fmol/mg tissue, n = 5, CGRP(8-37) group). In contrast to the atria, a lower and uniform density of CGRP receptors occurred in contractile tissue of the ventricular myocardium (e.g, 0.239 +/- 0.013 fnol/mg left ventricle, n = 5). The highest concentration of CGRP receptors in guinea pig cardiac tissue occurred at the bundle of His and the bundle branches (0.752 +/- 0.087 and 0.713 +/- 0.138 fmol/mg tissue, respectively n = 5). CGRP receptors were localized to coronary Vessels throughout the heart and to the ascending aorta and pulmonary trunk. Lastly, intracardiac ganglia exhibited moderate levels of specific [I-125]CGRP binding (0.475 +/- 0.043 fmolimg, n = 5), These Endings support the concept that CGRP can have direct effects on atrial and ventricular function as well as coronary now. The high density of CGRP receptors in the distal conducting system and the presence of CGRP receptors in intracardiac ganglia further suggest that CGRP could have important effects on cardiac conduction velocity and parasympathetic regulation of the heart. (C) 2001 Academic Press.