Adenosine and muscarinic cholinergic receptors attenuate cyclic AMP accumulation by different mechanisms in 1321N1 astrocytoma cells.
An adenosine receptor has been characterized to unambiguously demonstrate that the inhibitory guanine nucleotide regulatory protein, Gi, of 1321N1 human astrocytoma cells is fully capable of functionally coupling to adenylate cyclase. Adenosine receptor agonists attenuated cyclic AMP accumulation by 35 to 75% with the order of potency of N6(R-phenylisopropyl)-adenosine greater than adenosine = 2-chloroadenosine greater than N6-methyladenosine = N6-benzyladenosine. 3-Isobutyl-1-methylxanthine competitively antagonized the effect of adenosine receptor agonists. Adenylate cyclase activity measured in cell-free preparations from 1321N1 cells was inhibited by N6(R-phenylisopropyl)-adenosine. Pretreatment of 1321N1 cells with pertussis toxin blocked both adenosine receptor-mediated inhibition of adenylate cyclase activity and attenuation of cyclic AMP accumulation. In contrast to the effects on responses to adenosine receptor agonists, 3-isobutyl-1-methylxanthine noncompetitively antagonized muscarinic receptor-mediated attenuation of cyclic AMP accumulation and pertussis toxin had no effect. These data are consistent with the ideas that Gi is fully functional in 1321N1 cells and links inhibitory adenosine receptors to adenylate cyclase, and that the muscarinic receptor of these cells couples to the phosphoinositide response system, but is incapable of functionally coupling through Gi to inhibit adenylate cyclase.
A R
AR
Hughes
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Harden
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000378:metabolism; D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism*; D001254:Astrocytoma; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D037342:Pertussis Toxin; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology*; D011983:Receptors, Purinergic; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D011956:Receptors, Cell Surface; D011976:Receptors, Muscarinic; D011983:Receptors, Purinergic; D010566:Virulence Factors, Bordetella; D010660:Phenylisopropyladenosine; D000242:Cyclic AMP; D037342:Pertussis Toxin; D000243:Adenosine Deaminase; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D000241:Adenosine; D015056:1-Methyl-3-isobutylxanthine