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Cyclic AMP Analogues Potentiate k ‐Opiate and Attenuate α 2 ‐Adrenoceptor Agonist Effects on Intrasynaptosomal Free Calcium
Author(s) -
Adamson Peter,
Brammer Michael J.,
Campbell Iain 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.tb01072.x
Subject(s) - endocrinology , medicine , agonist , chemistry , adenosine , dynorphin , cyclase , adenylate kinase , cyclic adenosine monophosphate , dynorphin a , opiate , receptor , opioid peptide , biology , opioid
The intrasynaptosomal free calcium concentration ([Ca 2+ ] i ) was measured in quin2‐loaded synaptosomes prepared from rat cerebral cortex. Membrane‐permeant cyclic adenosine‐3′,5′‐monophosphate (cAMP) analogues [8‐bromo‐cyclic adenosine‐3′,5′‐monophosphate (8‐Br‐cAMP) and dibutyryl‐cyclic adenosine‐3′,5′‐monophosphate (db‐cAMP)] increased [Ca 2+ ] i in a dose‐dependent manner; The maximal increases were ˜50% for 8‐Br‐cAMP and 35% for db‐cAMP and occurred at ˜10 μ M with both analogues. Clonidine (1 μ M ) alone reduced [Ca 2+ ] i by 26.5%; db‐cAMP and 8‐Br‐cAMP attenuated this reduction to 14.2 and 8.2%, respectively. In contrast, the reduction (19.9%) in [Ca 2+ ] i induced by the preferential k ‐opiate agonist dynorphin A(1–13) was not attenuated by the cAMP analogues; in fact, db‐cAMP and 8‐Br‐cAMP potentiated the effect of dynorphin A(1–13) (1 μ M ), producing decreases in [Ca 2+ ] i of 33.6 and 29.6%, respectively. We conclude that although a r adrenergic and k ‐opiate receptors both reduce [Ca 2+ ] i , the α 2 ‐adrenoceptor‐mediated response and the k ‐opiate receptor‐mediated response involve different effector mechanisms. It appears that pre‐synaptic α 2 ‐adrenoceptor agonist effects are linked to reductions in adenylate cyclase activity and cAMP production and a resultant increase in Ca 2+ sequestration, Ca 2+ ‐channel blockade, or both. On the other hand, the k ‐opiate‐mediated effects possibly involve an increase in cAMP production and a blockade of Ca 2+ entry.