A study of extraneuronal uptake of norepinephrine in the perfused heart of the guinea-pig

Abstract

Guinea-pig hearts were perfused with large doses of norepinephrine (40 μg/ml) for 10 min and studied for localization of the amine by a histofluorescence method. Uptake of norepinephrine in the atria and ventricles was found to be localized primarily in 5 sites: adrenergic nerves, arterial smooth muscle, cardiac muscle, connective tissue fibers and interstitial cells which were identified as fibroblasts. Various agents were tested for their influence on norepinephrine uptake by first perfusion for 15 min followed by both norepinephrine and the drug for another 10 min. Those drugs that inhibited or reduced uptake of norepinephrine into vascular smooth muscle and fibroblasts were phenoxybenzamine, normetanephrine, metanephrine, guanethidine, bretylium, xylocholine (TM-10) and phentolamine. These drugs did not appear to have an effect on uptake of norepinephrine in adrenergic nerves, cardiac muscle or connective tissue. Drugs that had no effect on uptake of norepinephrine were MJ 1999, tranylcypromine, U-0521, α-methyl tyrosine, 3-methoxy-4-hydroxymandelic acid and tyrosine. Animals were also chronically treated with thyroxine, estradiol and prednisone. Only thyroxine-treated hearts showed a marked inhibitory effect on the uptake of norepinephrine in the fibroblasts and vascular smooth muscle. It is proposed that thyroid hormone increases the availability of catecholamine by extraneuronal inhibition of monoamine uptake by fibroblasts and blood vessels. It is suggested that fibroblasts and vascular muscle constitutes major sites for extraneuronal uptake and metabolism of catecholamines.