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Adenosine Inhibits Histamine‐Induced Phosphoinositide Hydrolysis Mediated via Pertussis Toxin‐Sensitive G Protein in Human Astrocytoma Cells
Author(s) -
Nakahata Norimichi,
Abe Marilene T.,
Matsuoka Isao,
Ono Tomoyuki,
Nakanishi Hironori
Publication year - 1991
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.1471-4159.1991.tb08244.x
Subject(s) - adenosine , pertussis toxin , inositol phosphate , inositol , adenosine receptor , histamine , g protein , adenosine a2b receptor , biochemistry , chemistry , adenosine a1 receptor , gtp' , phospholipase c , guanosine , biology , receptor , endocrinology , agonist , enzyme
The effect of adenosine on phosphoinositide hydrolysis was examined in 1321N1 human astrocytoma cells. Adenosine, L‐ N 6 ‐phenylisopropyladenosine ( l ‐PIA), and 5‐ ( N ‐ethylcarboxamido)adenosine (NECA) inhibited histaminc‐stimulated accumulation of inositol phosphates in a concentration‐dependent manner. The potency order of adenosine analogues for inhibition of inositol phosphate accumulation was l ‐PIA > adenosine > NECA, a finding indicating that A 1 ‐class adenosine receptors are involved in the inhibition. The reduction in inositol phosphate accumulation by l ‐PIA was blocked by an adenosine receptor antagonist, 8‐phenyltheophylline. Stimulation of A 1 ‐class adenosine receptors inhibited isoproterenol‐stimulated cyclic AMP accumulation as well as histamine‐induced inositol phosphate accumulation. Both inhibitory effects were blocked by pretreatment of the cells with pertussis toxin [islet‐activating protein (IAP)]. l ‐PIA also inhibited guanosine 5′‐(γ‐thio)triphosphate (GTPγ)‐stimulated accumulation of inositol phosphates in membrane preparations, and 8‐phenyltheophylline antagonized the inhibition. l ‐PIA could not inhibit GTPγS‐induced accumulation of inositol phosphates in IAP‐treated membranes. Gi/G 0 , purified from rabbit brain, inhibited GTPγS‐stimulated accumulation of inositol phosphates in a concentration‐dependent manner in membrane preparations. These results suggest that stimulation of A r class adenosine receptors interacts with the IAP‐sensitive G protein(s), resulting in the inhibitions of phospholipase C as well as adenylate cyclase in human astrocytoma cells.