Inhibitory and excitatory effects of micro-, delta-, and kappa-opioid receptor activation on breathing in awake turtles, Trachemys scripta.
For ectothermic vertebrates, such as reptiles, the effects of opioid receptor subtype activation on breathing are poorly understood. On the basis of previous studies on mammals and lampreys, we hypothesized that mu- and delta-opioid receptor (MOR and DOR, respectively) activation would cause respiratory depression, whereas kappa-opioid receptor (KOR) activation would have no effect. To address this question, we measured respiration in awake, freely swimming adult red-eared slider turtles (Trachemys scripta) before and after injection with agonists for specific opioid receptors. Injection of the MOR agonist [d-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin acetate salt (DAMGO, 1.5 or 6.5 mg/kg) decreased ventilation (Ve) by 72 +/- 9% and 95 +/- 3%, respectively, 4.0 h after injection as a result of decreased breathing frequency and no change in tidal volume (Vt). DOR agonists, such as [d-Pen(2,5)]-enkephalin hydrate (DPDPE, 5.0 mg/kg) and [d-Ala(2),d-Leu(5)]-enkephalin acetate salt (DADLE, 6.3 mg/kg), decreased Ve by 44 +/- 10% and 89 +/- 4%, respectively, 4.0 h after injection as a result of decreased breathing frequency and no change in Vt. DADLE also increased breath duration by a maximum of 25 +/- 9% at 6.0 h after injection. The KOR agonist U-50488 (6.2 mg/kg) increased Vt by a maximum of 52 +/- 30% at 5.0 h after injection, with variable nonsignificant changes in Ve and breathing frequency. Naloxone injections (0.25-0.5 mg/kg) 1.0 h before opioid agonist injections blocked all DAMGO-dependent effects, DPDPE-dependent frequency depression, and DADLE-dependent breath duration augmentation for 2.0 h after agonist injections. These results show that MOR and DOR activation causes respiratory depression as a result of decreased breathing frequency, whereas Vt is increased after KOR activation.
Johnson
Stephen M
SM
Dept. of Comparative Biosciences, School of Veterinary Medicine, Univ. of Wisconsin, 2015 Linden Dr., Madison, WI 53706, USA. johnsons@svm.vetmed.wisc.edu
Kinney
Matthew E
ME
Wiegel
Liana M
LM
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000818:Animals; D004594:Electrophysiology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000819:agonists*; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D017450:Receptors, Opioid, mu / Q000819:agonists*; D015656:Respiratory Mechanics / Q000187:drug effects; D013990:Tidal Volume / Q000187:drug effects; D014426:Turtles / Q000502:physiology*
D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D016308:Enkephalin, Leucine-2-Alanine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D020881:Enkephalin, D-Penicillamine (2,5)-