Role of mu 1- and delta-opioid receptors in modulation of fetal EEG and respiratory activity.
Recent evidence suggests that administration of low doses of morphine causes respiratory stimulation, along with a more active electroencephalogram (EEG) in the fetal lamb. The present study used selective opioid agonists and antagonists to determine the role mu 1- and delta-opioid receptor subtypes play in the response as well as determine if endogenous opioid peptides exert a tonic influence at the mu 1- and delta-opioid receptors to maintain normal EEG and respiratory activity under control, physiological conditions. Both morphine (2.5 mg/h iv) and [D-Pen2,D-Pen5]enkephalin (DPDPE) (46 nmol/h icv) resulted in a significant activation of fetal EEG, which was blocked by naloxonazine (NALZ, mu 1-opioid antagonist) and naltrindole (NTI, delta-opioid antagonist), respectively. Administration of NALZ alone, but not NTI, resulted in a slowing of the EEG. Morphine and [D-Ala2]deltorphin I (0.36 nmol/h icv) significantly increased breath number and were blocked by NALZ and NTI respectively. Both NALZ and NTI alone resulted in a reduction in breath number. These results suggest that the activation of the delta- or mu 1-opioid receptors will stimulate fetal respiratory and EEG activity. Furthermore, the endogenous opioids play a tonic role at both the delta- and mu 1-opioid receptors in the regulation of respiratory timing and EEG activity.
Cheng
P Y
PY
Department of Pharmacology, Cornell University Medical College, New York, New York 10021.
Wu
D
D
Soong
Y
Y
McCabe
S
S
Decena
J A
JA
Szeto
H H
HH
D000818:Animals; D004569:Electroencephalography; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D005324:Fetal Movement / Q000187:drug effects; D005333:Fetus / Q000502:physiology*; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000031:analogs & derivatives / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000502:physiology*; D012119:Respiration / Q000187:drug effects; D012756:Sheep
D004745:Enkephalins; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D009270:Naloxone; D009271:Naltrexone; D009020:Morphine; C034643:naloxonazine; D020881:Enkephalin, D-Penicillamine (2,5)-; C055382:naltrindole