Evidence for differential opioid mu 1- and mu 2-receptor-mediated regulation of heart rate in the conscious rat

Neuropharmacology. 1992 Aug;31(8):777-82. doi: 10.1016/0028-3908(92)90041-m.

Abstract

The possibility that mu-opioid-induced tachycardia and bradycardia could be mediated by different subtypes of the mu-receptor was studied in conscious Sprague-Dawley rats. The selective mu-receptor agonist dermorphin and its analog, TAPS (Tyr-D-Arg-Phe-sarcosine), a putative mu 1-receptor agonist, were given centrally. Tyr-D-Arg-Phe-sarcosine increased the heart rate, the response being inversely correlated to the dose (an increase of 71 +/- 22, 49 +/- 14 and 30 +/- 17 beats/min at doses of 0.3, 3 and 30 pmol, respectively). Dermorphin induced less clear changes in heart rate (maximum increase of 39 +/- 14 beats/min at the dose of 1 pmol). After treatment with the mu 1-selective antagonist naloxonazine (NAZ), TAPS 30 pmol and dermorphin 1 pmol decreased heart rate by -22 +/- 10 and -24 +/- 7 bpm, respectively. The bradycardiac effect of larger doses of dermorphin was potentiated by NAZ (from -25 +/- 8 to -97 +/- 22 bpm) but abolished by the non-selective antagonist naloxone. These data suggest that the high affinity mu 1-opioid receptors mediate tachycardic responses and mu 2-receptors mediate bradycardic responses.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analgesics, Opioid / antagonists & inhibitors
  • Analgesics, Opioid / pharmacology
  • Animals
  • Blood Pressure / drug effects
  • Heart Rate / physiology*
  • Injections, Intraventricular
  • Male
  • Naloxone / analogs & derivatives
  • Naloxone / pharmacology
  • Oligopeptides / antagonists & inhibitors
  • Oligopeptides / pharmacology
  • Opioid Peptides
  • Rats
  • Rats, Inbred Strains
  • Receptors, Opioid / physiology*
  • Receptors, Opioid, mu

Substances

  • Analgesics, Opioid
  • Oligopeptides
  • Opioid Peptides
  • Receptors, Opioid
  • Receptors, Opioid, mu
  • dermorphin
  • Naloxone
  • naloxonazine