alpha-2-Adrenergic activation of proopiomelanocortin-containing neurons in the arcuate nucleus causes opioid-mediated hypotension and bradycardia.

Treatment of rats for 4 days with alpha-methyldopa, 200 mg/kg/day i.p., increases steady state levels of proopiomelanocortin (POMC) mRNA in the mediobasal hypothalamus, as measured by DNA excess solution hybridization. The increase is prevented by parallel treatment with yohimbine, 2 mg/kg/day i.p., but not by naltrexone, 2 mg/kg/day i.p. Treatment with the peripheral vasodilator hydralazine, 2 mg/kg/day, does not affect POMC mRNA levels. In situ hybridization histochemistry with a cRNA probe for POMC indicates that POMC-containing cells are located within the confines of the arcuate nucleus both in control and in alpha-methyldopa-treated rats, and confirms the increase in POMC mRNA in the latter. Microinjection of 2 micrograms of alpha-methylnorepinephrine unilaterally into the arcuate nucleus of urethane-anesthetized rats causes hypotension and bradycardia, which can be inhibited by 200 ng of yohimbine microinjected into the same site, or by 100 ng l-naloxone microinjected into the ipsilateral nucleus tractus solitarii, but not into the arcuate nucleus. These findings are interpreted to indicate that activation of alpha 2-adrenergic receptors located on POMC-containing neurons in the arcuate nucleus causes beta-endorphin release and stimulation of opiate receptors in the NTS, which results in hypotension and bradycardia, and that this mechanism contributes to the hypotensive action of alpha-methyldopa.
AuthorsS J Li, M N Scanlon, Z Járai, K Varga, N S Gantenberg, E Lazar-Wesley, G Kunos
JournalNeuroendocrinology (Neuroendocrinology) Vol. 63 Issue 3 Pg. 275-83 (Mar 1996) ISSN: 0028-3835 [Print] SWITZERLAND
PMID8677016 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Adrenergic alpha-Agonists
  • RNA, Messenger
  • Receptors, Adrenergic, alpha
  • Yohimbine
  • Methyldopa
  • beta-Endorphin
  • Pro-Opiomelanocortin
  • Nordefrin
  • Adrenergic alpha-Agonists (administration & dosage, pharmacology)
  • Animals
  • Arcuate Nucleus of Hypothalamus (drug effects, physiopathology)
  • Bradycardia (chemically induced, physiopathology)
  • Hypotension (chemically induced, physiopathology)
  • In Situ Hybridization
  • Male
  • Methyldopa (pharmacology)
  • Microinjections
  • Neurons (physiology)
  • Nordefrin (administration & dosage, pharmacology)
  • Pro-Opiomelanocortin (genetics, metabolism)
  • RNA, Messenger (metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, alpha (drug effects, physiology)
  • Yohimbine (pharmacology)
  • beta-Endorphin (pharmacology)

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