Distribution of alpha 1-adrenergic receptors in myocytic regions and vasculature of feline myocardium.
The physiological and pathophysiological roles of myocardial alpha 1-adrenergic receptors are not clearly defined. To delineate the distribution of alpha 1-receptors in myocytic and vascular components of the heart, we characterized the binding of [3H]prazosin to alpha 1-receptors in unfixed, transmural slices of feline left ventricle. Specific binding ratios greater than 95% were achieved at radioligand concentrations near the dissociation constant (Kd). Binding of radioligand to receptors in transmural slices was rapid, reversible, saturable, stereoselective, and displaceable by subtype-selective antagonists with a rank order of potency characteristic of alpha 1-receptors. Analysis of binding isotherms indicated a Bmax of 9.1 +/- 1.9 fmol/mg protein and a Kd of 36.9 +/- 6.3 pM. Results of light microscopic autoradiography indicated that regions composed of closely arranged cardiac myocytes contained three to fourfold more alpha 1-receptors per unit section area than the resistance microvasculature, which in turn contained approximately twice the density of alpha 1-receptors observed in the medial smooth muscle of large conductance arteries. No differences in the density of alpha 1-receptors between subepicardial and subendocardial regions were observed for either myocytic regions or coronary arterioles. These results indicate that myocytic regions of the cat ventricle contain a high density of alpha 1-adrenergic receptors. The methods developed should be of value in characterizing the distribution and function of alpha 1-receptors and mechanisms of regulation of adrenergic responsiveness in intact myocyardium.
Saffitz
J E
JE
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
D000818:Animals; D001345:Autoradiography; D002415:Cats; D003331:Coronary Vessels / Q000032:analysis*; D009206:Myocardium / Q000032:analysis*; D011224:Prazosin / Q000378:metabolism; D011869:Radioligand Assay; D011942:Receptors, Adrenergic, alpha / Q000032:analysis*
D011942:Receptors, Adrenergic, alpha; D011224:Prazosin