Characterization of opioid receptors in the cat carotid body involved in chemosensory depression in vivo.
The effects of selective opioid receptor agonists and antagonists on neural discharge recorded from carotid body arterial chemoreceptors in vivo were studied in anaesthetized cats. Mean ID50 values were determined for each agonist and used to assess chemodepressant potency on intracarotid (i.c.) injection in animals artificially ventilated with air. [Met]enkephalin, [Leu]enkephalin, [D-Ala2, D-Leu5]enkephalin and [D-Pen2, D-Pen5]enkephalin were more potent chemodepressants than [D-Ala2, Me-Phe4, Gly-ol5]enkephalin, dynorphin (1-8) or ethylketocyclazocine; morphiceptin (mu-agonist) was inactive. The rank order of potency was compatible with the involvement of delta-opioid receptors in opioid-induced depression of chemosensory discharge. ICI 154129, a delta-opioid receptor antagonist, was used in fairly high doses and caused reversible dose-related antagonism of chemodepression induced by [Met]enkephalin. It also antagonized depression caused by single doses of [Leu]enkephalin, [D-Ala2, D-Leu5]enkephalin, [D-Ala2, Me-Phe4, Gly-ol5]enkephalin or dynorphin (1-8). ICI 174864, a more potent and selective delta-opioid receptor antagonist, also antagonized chemodepression induced by [Met]enkephalin or by the selective delta-receptor agonist [D-Pen2, D-Pen5]enkephalin. Comparison of background or 'spontaneous' chemosensory discharge during the 30 min periods immediately before and after injecting ICI 174864 (0.1-0.2 mg kg-1 i.c.) showed a significant increase in discharge in one experiment, but in four others discharge was either unaffected or decreased after the antagonist, which argues against a toxic depression of chemosensors by endogenous opioids under resting conditions in our preparation. Sensitivity of the carotid chemoreceptors to hypoxia (ventilating with 10% O2) was increased significantly after ICI 174864, which could be taken as evidence that endogenous opioids depress chemosensitivity during hypoxia. In contrast, responsiveness to hypercapnia was reduced after the antagonist, implying that endogenous opioids may potentiate chemoreceptor sensitivity during hypercapnia. The results obtained using 'selective' agonists and antagonists provide evidence that depression of chemosensory discharge caused by injected opioids involves a delta type of opioid receptor within the cat carotid body. Endogenous opioids may modulate arterial chemoreceptor sensitivity to physiological stimuli such as hypoxia and hypercapnia.
D000818:Animals; D002344:Carotid Body / Q000502:physiology*; D002415:Cats; D002628:Chemoreceptor Cells / Q000502:physiology*; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000494:pharmacology; D004723:Endorphins / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D004744:Enkephalin, Methionine / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology; D016314:Ethylketocyclazocine; D006935:Hypercapnia / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D010446:Peptide Fragments / Q000494:pharmacology; D011957:Receptors, Opioid / Q000502:physiology*
D004723:Endorphins; D004745:Enkephalins; D010446:Peptide Fragments; D011957:Receptors, Opioid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004744:Enkephalin, Methionine; D016314:Ethylketocyclazocine; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; D004399:Dynorphins; C026770:dynorphin (1-8); D020881:Enkephalin, D-Penicillamine (2,5)-; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine; C036405:ICI 154129; C028889:morphiceptin; D003496:Cyclazocine