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Activation of the Prostanoid EP3 Receptor Mediates Central Nicotinic Acid‐Evoked Pressor Response in Conscious Rats
Author(s) -
Rezq Samar,
AbdelRahman Abdel
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.623.4
Subject(s) - rostral ventrolateral medulla , chemistry , medicine , receptor , endocrinology , glutamate receptor , nmda receptor , medulla oblongata , central nervous system , biology , biochemistry
Nicotinic acid (NA) produces prostaglandins (PGs)‐dependent flushing via GPR109A activation. Although NA crosses the blood brain barrier, there are no reports on GPR109A expression or function in blood pressure (BP) controlling nuclei; e.g. the rostral ventrolateral medulla (RVLM). We built on GPR109A expression in the RVLM by showing in conscious rats that intra‐RVLM NA (20 µg/rat) led to a biphasic BP elevation. The first pressor phase (within 1 min of NA injection) resembled intra‐RVLM L‐glutamate mediated pressor response, and was abolished by the N‐methyl‐D‐aspartate receptor (NMDAR) blocker (2‐amino‐5‐phosphonopentanoic acid; AP5). We hypothesized that the longer lasting second pressor phase (5‐15 min after NA injection) is mediated via local PGs release. The finding that the prostanoid EP3 receptor subtype blocker L‐798106 abolished the NA‐evoked delayed pressor response supported our hypothesis. NA increased L‐glutamate level in PC12 cells, which exhibit neuronal phenotype and express GPR109A. The BP and biochemical effects are GPR109A dependent because they were not reproduced by the NA isomer isonicotinic acid, which lakes the receptor activity. These novel findings suggest that both L‐glutamate and PGs release are involved in NA‐mediated pressor response and that GPR109A is the main target for NA central actions. Ongoing GPR109A knockout studies, direct measurements of PGs levels, and the effect of other EP receptor blockers on NA‐mediated pressor response will solidify the molecular mechanisms implicated in RVLM GPR109A involvement in BP regulation. The present findings are clinically relevant because they elucidate a mechanistic role for GPR109A in the central BP regulation and highlight central GPR109A blockade as a potential antihypertensive strategy.