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Activation of central nicotinic acid receptor GPR109A increases blood pressure in conscious rats (841.11)
Author(s) -
Rezq Samar,
AbdelRahman Abdel
Publication year - 2014
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.28.1_supplement.841.11
Subject(s) - rostral ventrolateral medulla , glutamate receptor , chemistry , medulla oblongata , nmda receptor , pharmacology , medicine , endocrinology , receptor , central nervous system , biology , biochemistry
The hypolipidemic drug nicotinic acid (NA) elicits prostaglandins (PGs)‐dependent flushing reaction via GPR109A activation. There are no reports on GPR109A expression or function in the rostral ventrolateral medulla (RVLM), despite evidence that NA reaches the brain. We present the first evidence for GPR109A expression in the RVLM (Western blot). Next, we showed in conscious rats that intra‐RVLM NA (estimated doses to reach the RVLM following systemic administration) increased BP and reduced HR, which resembled responses elicited by intra‐RVLM L‐glutamate. The pressor effect of NA was abolished by selective NMDAR blockade (2‐amino‐5‐phosphonopentanoic acid; AP5) and enhanced by L‐glutamate uptake inhibition (L‐trans‐Pyrrolidine‐2,4‐dicarboxylic acid; PDC). Further NA elevated L‐glutamate level in culture medium of PC12 cells, which exhibit neuronal phenotype and express GPR109A. These novel findings suggest that L‐glutamate release is involved in RVLM GPR109A‐mediated brief pressor response. Ongoing integrative and molecular studies will elucidate the role of PGs and oxidative stress in the delayed pressor response caused by intra‐RVLM NA. The findings are clinically relevant because they elucidate the mechanisms of a centrally mediated deleterious effect of NA on BP, and yield new insight into the potential use of concurrent therapeutics to circumvent such deleterious effect.