Mutual antagonism of kappa-opiate and alpha 2-adrenoceptor agonist effects on intrasynaptosomal free [Ca2+]i.
Synaptosomes prepared from rat cerebral cortices on Percoll discontinuous density gradients were loaded with the fluorescent EGTA analogue Quin 2 to allow measurement of intracellular free [Ca2+]i. When either kappa-opiate or alpha 2-adrenoceptor agonists were incubated with the synaptosomes, there was a highly significant (p less than 0.004, p less than 2.7 X 10(-6), respectively) reduction in intrasynaptosomal free [Ca2+]i relative to controls. As these synaptosomes are not depolarised, the data suggest that both alpha 2-adrenoceptor agonists and kappa-opiate agonists inhibit neurotransmitter release, decreasing the availability of intraneuronal [Ca2+]i rather than altering Ca2+ entry. However, when these two agonists were coincubated, there was a complete abolition of the effects of either agonist; in fact, there was an apparent increase in the intrasynaptosomal free [Ca2+]i. Neither morphine nor [D-Ala2-D-Leu5]enkephalin, mu and delta opiate agonists respectively, had any significant effect on intrasynaptosomal free [Ca2+]i. These results show that the individual effects of clonidine and dynorphin A1-13 are in keeping with the role of these substances at autoreceptors controlling neurotransmitter release. The mutual antagonism of their effects on [Ca2+]i is more difficult to explain but it may be a mechanism that prevents the occurrence of excessive inhibition of neuronal systems.
D000634:Aminoquinolines; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002540:Cerebral Cortex / Q000648:ultrastructure*; D003000:Clonidine / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D004399:Dynorphins / Q000494:pharmacology; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D005456:Fluorescent Dyes; D019329:Idazoxan; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017473:Receptors, Opioid, kappa; D013574:Synaptosomes / Q000378:metabolism*
D000634:Aminoquinolines; D004146:Dioxanes; D005456:Fluorescent Dyes; D010446:Peptide Fragments; D011942:Receptors, Adrenergic, alpha; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D009270:Naloxone; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; C026843:dynorphin (1-13); D004399:Dynorphins; D009020:Morphine; D003000:Clonidine; C035739:Quin2; D002118:Calcium; D019329:Idazoxan