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Mutual Antagonism of κ‐Opiate and α 2 ‐Adrenoceptor Agonist Effects on Intrasynaptosomal Free [Ca 2+ ] i
Author(s) -
Adamson P.,
McWilliam J. R.,
Brammer M. J.,
Campbell I. C.
Publication year - 1988
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1988.tb13230.x
Subject(s) - chemistry , agonist , autoreceptor , neurotransmitter , endocrinology , medicine , synaptosome , enkephalin , opiate , egta , biophysics , receptor , calcium , opioid , biology , biochemistry , in vitro , organic chemistry
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 [Ca 2+ ] i . When either κ‐opiate or α 2 ‐adrenoceptor agonists were incubated with the synaptosomes, there was a highly significant (p < 0.004, p < 2.7 × 10 −6 , respectively) reduction in intrasynaptosomal free [Ca 2+ ] i relative to controls. As these synaptosomes are not depolarised, the data suggest that both α 2 ‐adrenoceptor agonists and κ‐opiate agonists inhibit neurotransmitter release, decreasing the availability of intraneuronal [Ca 2+ ] i rather than altering Ca 2+ 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 [Ca 2+ ] i . Neither morphine nor [D‐Ala 2 ‐D‐Leu 5 ]enkephalin, μ and δ opiate agonists respectively, had any significant effect on intrasynaptosomal free [Ca 2+ ] i . These results show that the individual effects of clonidine and dynorphin A 1–13 are in keeping with the role of these substances at autoreceptors controlling neurotransmitter release. The mutual antagonism of their effects on [Ca 2+ ] i is more difficult to explain but it may be a mechanism that prevents the occurrence of excessive inhibition of neuronal systems.