Studies on the opiate receptor-mediated inhibition of K+-stimulated cholecystokinin and substance P release from cat hypothalamus in vitro.
The addition of 50 mM K+ to the perfusate of cat hypothalamic slices results in a 3.4- and 5.5-fold increase in the levels of cholecystokinin (CCK) and substance P (sP) like immunoreactivity, respectively. The addition of morphine (10(-11)-10(-8) M; a mu receptor agonist) and D-Ala2-D-Leu5-enkephalin (DADL: 10(-12)-10(-10) M; a delta receptor agonist) resulted in a dose-dependent suppression of the K+-evoked release. SKF10047 (a sigma receptor ligand) and U50488H (a kappa receptor ligand) had no effect in doses up to 10(-6) M. Naloxone added with the lowest dose of agonist producing a maximal inhibition produced a dose-dependent reversal of the anti-release effects of morphine and DADL. The IC50 of naloxone for the antagonism by DADL and morphine of the release of CCK were similar, whereas the naloxone IC50 was lower for morphine than DADL in the reversal of the effects of the agonist in sP release. Within the constraints of receptor selectivity of the several ligands, these data suggest that at least two populations of opioid receptors (mu and delta) may be discriminated which govern the release of hypothalamic sP.
D000818:Animals; D002415:Cats; D002766:Cholecystokinin / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004743:Enkephalin, Leucine / Q000008:administration & dosage / Q000031:analogs & derivatives; D016308:Enkephalin, Leucine-2-Alanine; D007031:Hypothalamus / Q000378:metabolism*; D009020:Morphine / Q000008:administration & dosage; D009270:Naloxone / Q000008:administration & dosage; D011188:Potassium / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000502:physiology*; D013373:Substance P / Q000378:metabolism*
D011957:Receptors, Opioid; D013373:Substance P; D009270:Naloxone; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; D009020:Morphine; D002766:Cholecystokinin; D011188:Potassium