INFLUENCE OF SYMPATHETIC NERVE STIMULATION ON CONVERSION OF H³-TYROSINE TO H³-CATECHOLAMINE AND ON H³-NOREPINEPHRINE DISPOSITION IN RABBIT PULMONARY ARTERY

¹ Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut

Stimulation of the sympathetic innervation of rabbit pulmonary artery in vitro, at a rate of 5 cps, significantly reduced conversion of H³-tyrosine to H³-dopamine and H³-norepinephnine (NE) within the tissue, when compared to that in unstimulated arteries. Stimulation at a frequency of 25 cps resulted in enhancement of synthesis if the total newly synthesized catecholamine was calculated by adding amine retained by the tissue to that lost to the bathing fluid during nerve stimulation. The NE lost from unstimulated arteries was almost entirely newly synthesized material. As the frequency of nerve stimulation was increased, the amount of endogenous NE lost during stimulation increased until, at 25 cps, 60% of the total lost was endogenous amine. Density-gradient centrifugation of sucrose homogenates, prepared from sympathetically innervated rabbit pulmonary artery incubated for one hour with H³-NE, revealed two peaks of radioactivity. Subcellular elements, corresponding to these peaks, sedimented at 0.5 M sucrose (``light'' fraction) and 1.0 to 12 M sucrose (``heavy'' fraction). Sympathetic nerve stimulation at 5 cpa or 25 cpa during incubation with H³-NE significantly increased the ratio of H³-NE in light fraction to H³-NE in heavy fraction when compared to unstimulated control preparations. The relative shift of H³-NE into the light fraction may reflect a change in NE subcellular distribution that accompanies sympathetic nerve activity.