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Adenosine Receptors Mediating Cyclic AMP Productioin the Rat Hippocampus
Author(s) -
Fredholm Bertil B.,
Jonzon Bror,
Lindgren Eva,
Lindström Karin
Publication year - 1982
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.1471-4159.1982.tb04715.x
Subject(s) - adenosine , adenosine receptor , adenosine deaminase , adenosine a1 receptor , medicine , adenosine a2b receptor , purinergic signalling , endocrinology , chemistry , adenosine deaminase inhibitor , receptor , biology , biochemistry , agonist
In the transversely cut rat hippocampus, adenosine caused a dose‐dependent increase in the accumulation of [ 3 H]cyclic AMP from [ 3 H]ATP. Adenosine breakdown products were inactive. AMP was somewhat less effective than adenosine, and its effect could be partially, but not completely, abolished by α,β‐methylene‐ADP and GMP, which inhibited its metabolism by 5′‐nucleotidase. The effect of adenosine was unaffected by inhibitors of adenosine deaminase, but enhanced by several inhibitors of adenosine uptake. Some analogues of adenosine, including N 6 ‐phenylisopropyladenosine (PIA), 2‐chloroadenosine and adenosine 5′‐ethylcarboxamide (NECA), were more active than adenosine, whereas others such as 2‐deoxyadenosine and 9‐(tetrahydro‐2‐furyl)adenine (SQ 22536) actually inhibited the response. The effect of PIA was highly stereospecific. The action of adenosine was inhibited by several alkylxanthines, the most potent of which was 8‐phenyltheophylline. [ 3 H]Cyclohexyladenosine (CHA) bound specifically to cell membranes from the rat hippocampus. The extent of binding was similar to that found in other cortical areas. The relative potency of some adenosine analogues and alkylxanthines to displace labelled CHA was essentially similar to their potency as effectors of the cyclic AMP system. Adenosine contributed to the cyclic AMP‐elevating effect of α‐adrenoceptor‐stimulating drugs and several amino acids, but not to that seen with isoprenaline. The cyclic AMP increase seen following depolarization was only partially adenosine‐dependent. The present results demonstrate that the rat hippocampus contains adenosine receptors mediating cyclic AMP accumulation and that these receptors have similar characteristics to those mediating pyramidal cell depression. Adenosine‐induced cyclic AMP accumulation may be used as a biochemical correlate to electrophysiology and as a convenient parameter to assess the influence of drugs on adenosine mechanisms in the rat hippocampus.