Abstract
BackgroundThe polyunsaturated fatty acid, docosahexaenoic acid (DHA), participates in neurotransmission involving activation of calcium-independent phospholipase A2 (iPLA2), which is coupled to muscarinic, cholinergic and serotonergic neuroreceptors. Drug induced activation of iPLA2 can be measured in vivo with quantitative autoradiography using 14C-DHA as a probe. The present study used this approach to address whether a DHA signal is produced following dompaminergic (D)2-like receptor activation with quinpirole in rat brain. Unanesthetized rats were infused intravenously with 14C-DHA one minute after saline or quinpirole infusion, and serial blood samples were collected over a 20-minute period to obtain plasma. The animals were euthanized with sodium pentobarbital and their brains excised, coronally dissected and subjected to quantitative autoradiography to derive the regional incorporation coefficient, k*, a marker of DHA signaling. Plasma labeled and unlabeled unesterified DHA concentrations were measured.ResultsThe incorporation coefficient (k*) for DHA did not differ significantly between quinpirole-treated and control rats in any of 81 identified brain regions. Plasma labeled DHA concentration over the 20-minute collection period (input function) and unlabeled unesterified DHA concentration did not differ significantly between the two groups.ConclusionThese findings demonstrate that D2-like receptor initiated signaling does not involve DHA as a second messenger, and likely does not involve iPLA2 activation.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2202-15-113) contains supplementary material, which is available to authorized users.
Highlights
The polyunsaturated fatty acid, docosahexaenoic acid (DHA), participates in neurotransmission involving activation of calcium-independent phospholipase A2, which is coupled to muscarinic, cholinergic and serotonergic neuroreceptors
The polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (22:6n-3, DHA) and arachidonic acid (20:4n-6, Arachidonic acid (AA)) are important second messengers in brain, where they participate in neurotransmission [2]
Agonist binding to certain neuroreceptors can release AA or DHA from the stereospecifically numbered-2 position of membrane phospholipids via activation of AA-selective group IVA calcium-dependent cytosolic phospholipase A2 or DHA-selective group VIA calcium-independent
Summary
Physiological parameters One control rat died after surgery and prior to infusion with saline due to unknown causes. Heart rate and systolic and diastolic blood pressure did not differ significantly (P > 0.05 by unpaired t-test). Heart rate and systolic and diastolic blood pressures did not significantly change after saline or quinpirole injection, compared to baseline (P > 0.05 by paired t-test). Mean integral radioactivity over time, which represents the input function, did not differ significantly between saline and quinpirole treated rats (quinpirole, 183834 ± 51257 nCi/ml/s, n = 7 versus saline, 184872 ± 49596 nCi/ml/s, n = 6), consistent with our previous report [38]. Incorporation rate (Jin) Regional rates of unesterified DHA incorporation into the brain, calculated from the product of k* and unesterified plasma DHA concentration (2), did not differ significantly between the groups in the 81 regions examined (data not shown). Mean Jin values in vehicle and quinpirole treated rats were 58.8 ± 20.8 and 73.6 ± 22.5 nmol/s/g×10−4, respectively (P >0.05 by unpaired t-test)
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