title: Ser/thr phosphatases tonically attenuate the ERK-dependent pressor effect of ethanol in the rostral ventrolateral medulla in normotensive rats.
abstract: We recently reported that microinjection of ethanol into the rostral ventrolateral medulla (RVLM) elicits modest increases in local extracellular signal-regulated kinase (ERK) and blood pressure (BP) in conscious normotensive rats. In this study, we tested the hypothesis that RVLM ser/thr phosphatases dampen the ERK-dependent pressor effect of ethanol in normotensive rats. We show that the pressor response elicited by intra-RVLM ethanol (10 μg) was (i) abolished following local ERK inhibition with PD98059 (1 μg) and (ii) associated with significant reduction in local phosphatase activity. Inhibition of the RVLM ser/thr phosphatase activity by okadaic acid (OKA, 0.4 μg) or fostriecin (15 pg) caused significant increases in blood pressure (BP) and potentiated the magnitude and duration of the pressor response as well as the phosphatase inhibition elicited by subsequent intra-RVLM administration of ethanol. Intra-RVLM acetaldehyde (2 μg), the main metabolic product of ethanol, caused no changes in BP or RVLM phosphatase activity but it produced significant increases in BP and inhibition of local phosphatase activity in rats treated with OKA or fostriecin. Together, the RVLM phosphatase activity acts tonically to attenuate the ERK-dependent pressor effect of ethanol or acetaldehyde in normotensive rats.
authors: Department of Pharmacology and Toxicology, School of Medicine, East Carolina University, Greenville, NC, USA. Electronic address: mahelm@hotmail.com.
authors: Mahmoud M
authors: MM
authors: El-Mas
authors: Department of Pharmacology and Toxicology, School of Medicine, East Carolina University, Greenville, NC, USA. Electronic address: abdelrahmana@ecu.edu.
authors: Abdel A
authors: AA
authors: Abdel-Rahman
mesh_terms: D000079:Acetaldehyde / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000201:enzymology; D019319:Okadaic Acid / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011090:Polyenes / Q000494:pharmacology; D011753:Pyrones / Q000494:pharmacology; D011921:Rats, Inbred WKY; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D005419:Flavonoids; D011090:Polyenes; D011753:Pyrones; D014662:Vasoconstrictor Agents; D019319:Okadaic Acid; D000431:Ethanol; D048049:Extracellular Signal-Regulated MAP Kinases; D010744:Phosphoric Monoester Hydrolases; D000079:Acetaldehyde; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; C040313:fostriecin
keywords: Ethanol; Extracellular signal-regulated kinase; Hypertension; Normotensive rats; Phosphatases; Rostral ventrolateral medulla