Alpha-2-adrenergic activation of proopiomelanocortin-containing neurons in the arcuate nucleus causes opioid-mediated hypotension and bradycardia

Si Jia Li, Martin N. Scanlon, Z. Járai, Károly Varga, Nicholas S. Gantenberg, Eliane Lazar-Wesley, George Kunos

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Treatment of rats for 4 days with α-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 α-methyldopa-treated rats, and confirms the increase in POMC mRNA in the latter. Microinjection of 2 μg of α-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 α2-adrenergic receptors located on POMC-containing neurons in the arcuate nucleus causes β-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 α-methyldopa.

Original languageEnglish
Pages (from-to)275-283
Number of pages9
JournalNeuroendocrinology
Volume63
Issue number3
Publication statusPublished - Mar 1996

Fingerprint

Pro-Opiomelanocortin
Arcuate Nucleus of Hypothalamus
Bradycardia
Adrenergic Agents
Hypotension
Opioid Analgesics
Neurons
Methyldopa
Yohimbine
Messenger RNA
Nordefrin
Endorphins
Hydralazine
Complementary RNA
Naltrexone
Solitary Nucleus
Urethane
Microinjections
Opioid Receptors
Naloxone

Keywords

  • Beta-endorphin
  • Blood pressure
  • Catecholamine receptors
  • Opiate peptides
  • Proopiomelancortin

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)

Cite this

Alpha-2-adrenergic activation of proopiomelanocortin-containing neurons in the arcuate nucleus causes opioid-mediated hypotension and bradycardia. / Li, Si Jia; Scanlon, Martin N.; Járai, Z.; Varga, Károly; Gantenberg, Nicholas S.; Lazar-Wesley, Eliane; Kunos, George.

In: Neuroendocrinology, Vol. 63, No. 3, 03.1996, p. 275-283.

Research output: Contribution to journalArticle

Li, Si Jia ; Scanlon, Martin N. ; Járai, Z. ; Varga, Károly ; Gantenberg, Nicholas S. ; Lazar-Wesley, Eliane ; Kunos, George. / Alpha-2-adrenergic activation of proopiomelanocortin-containing neurons in the arcuate nucleus causes opioid-mediated hypotension and bradycardia. In: Neuroendocrinology. 1996 ; Vol. 63, No. 3. pp. 275-283.
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abstract = "Treatment of rats for 4 days with α-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 α-methyldopa-treated rats, and confirms the increase in POMC mRNA in the latter. Microinjection of 2 μg of α-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 α2-adrenergic receptors located on POMC-containing neurons in the arcuate nucleus causes β-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 α-methyldopa.",
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AU - Li, Si Jia

AU - Scanlon, Martin N.

AU - Járai, Z.

AU - Varga, Károly

AU - Gantenberg, Nicholas S.

AU - Lazar-Wesley, Eliane

AU - Kunos, George

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AB - Treatment of rats for 4 days with α-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 α-methyldopa-treated rats, and confirms the increase in POMC mRNA in the latter. Microinjection of 2 μg of α-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 α2-adrenergic receptors located on POMC-containing neurons in the arcuate nucleus causes β-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 α-methyldopa.

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