Comparison of the effects of calcium concentration on mu and kappa agonist actions in the guinea pig ileum.
The effect of calcium on responses to selective mu (fentanyl and DAGO) and selective kappa agonists was investigated on guinea pig ileum. The dose-response curves were shifted to the right in a non-parallel fashion with increasing calcium concentration (0.9-3.6 mM). However U50488 was shifted more than either fentanyl or DAGO. Both fentanyl and U50488 could not produce 100% inhibition of twitch in 3.6 mM calcium. It is concluded that the efficacy of the agonists changes with calcium concentration and that the kappa agonist U50488 is affected more than the mu agonists because kappa receptor activation directly inhibits calcium entry whereas mu receptors inhibit calcium by increasing potassium conductance.
Johnson
M A
MA
Parke-Davis Research Unit, Addenbrookes Hospital site, Cambridge, UK.
Hill
R G
RG
Hughes
J
J
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology*; D005283:Fentanyl / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu
D004745:Enkephalins; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D002118:Calcium; D005283:Fentanyl