期刊
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
卷 314, 期 3, 页码 945-952出版社
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/jpet.105.087510
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资金
- NIAAA NIH HHS [R01 AA007839, AA 07839] Funding Source: Medline
- NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM [R29AA007839, R01AA007839] Funding Source: NIH RePORTER
Our previous study showed that rilmenidine, a selective I-1-imidazoline receptor agonist, enhanced the phosphorylation of mitogen-activated protein kinase (MAPK)(p42/44), via the phosphatidylcholine-specific phospholipase C pathway in the pheochromocytoma cell line (PC12). In the present study, we tested the hypothesis that enhancement of MAPK phosphorylation in the rostral ventrolateral medulla (RVLM) contributes to the hypotensive response elicited by I-1-receptor activation in vivo. Systemic rilmenidine (600 mu g/kg i.v.) elicited hypotension and bradycardia along with significant elevation in MAPK(p42/44), detected by immunohistochemistry, in RVLM neurons. To obtain conclusive evidence that the latter response was I-1-receptor-mediated, similar hypotensive responses were elicited by intracisternal (i.c.) rilmenidine (25 mu g/rat) or the highly selective alpha(2)-agonist alpha-methylnorepinephrine (4 mu g/rat). An increase in RVLM MAPK(p42/44) occurred only after rilmenidine. Furthermore, pretreatment with efaroxan (0.15 mu g/rat i.c.), a selective I-1-imidazoline receptor antagonist, or with PD98059 (2'-amino-3'-methoxyflavone) (5 mu g/rat i.c.), a selective extracellular signal-regulated kinase 1/2 inhibitor, significantly attenuated the hypotensive response and the elevation in RVLM MAPK(p42/44) elicited by i.c. rilmenidine. The findings suggest that MAPK phosphorylation in the RVLM contributes to the hypotensive response induced by I-1-receptor activation and presents in vivo evidence that distinguishes the neuronal responses triggered by the I-1-receptor from those triggered by the alpha(2)-adrenergic receptor.
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