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1Section on Brain Physiology and Metabolism, National Institute on Aging, National Institutes of Health, Bethesda, Maryland; 2Department of Pathology, Saint Louis University, St. Louis, Missouri; and 3Department of Pharmacology, Physiology, and Therapeutics, and Department of Chemistry, University of North Dakota, Grand Forks, North Dakota
Submitted 16 June 2004 ; accepted in final form 18 January 2005
Heart sympathetic denervation can accompany Parkinson's disease, but the effect of this denervation on cardiac lipid-mediated signaling is unknown. To address this issue, rats were sympathetically denervated with 6-hydroxydopamine (6-OHDA, 50 mg/kg ip) and infused with 170 µCi/kg of either [1-14C]palmitic acid ([1-14C]16:0) or [1-14C]arachidonic acid ([1-14C]20:4 n-6), and kinetic parameters were assessed using a steady-state radiotracer model. Heart norepinephrine and epinephrine levels were decreased 82 and 85%, respectively, in denervated rats, and this correlated with a 34% reduction in weight gain in treated rats. Fatty acid tracer uptake was not significantly different between groups for either tracer, although the dilution coefficient
was increased in [1-14C]20:4 n-6-infused rats, which indicates that less 20:4 n-6 was recycled in denervated rats. In [1-14C]16:0-infused rats, incorporation rate and turnover values of 16:0 in stable lipid compartments were unchanged, which is indicative of preservation of
-oxidation. In [1-14C]20:4 n-6-infused rats, there were dramatic reductions in incorporation rate (6084%) and turnover value (5685%) in denervated rats that were dependent upon the lipid compartment. In addition, phospholipase A2 activity was reduced 40% in treated rats, which is consistent with the reduction observed in 20:4 n-6 turnover. These results demonstrate marked reductions in 20:4 n-6 incorporation rate and turnover in sympathetic denervated rats and thereby suggest an effect on lipid-mediated signal transduction mediated by a reduction in phospholipase A2 activity.
palmitic acid; signal transduction; phospholipase A2; catecholamines; phospholipids
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