A1 and A2 adenosine receptors in rabbit cortical collecting tubule cells. Modulation of hormone-stimulated cAMP

L. J. Arend, W. K. Sonnenburg, W. L. Smith, W. S. Spielman

Research output: Contribution to journalArticle

Abstract

Adenosine analogs were used to investigate the cellular mechanisms by which adenosine may alter renal tubular function. Cultured rabbit cortical collecting tubule (RCCT) cells, isolated by immunodissection, were treated with 5'-N-ethylcarboxamideadenosine (NECA), N6-cyclohexyladenosine (CHA), and R-N6-phenylisopropyladenosine (PIA). All three analogs produced both dose-dependent inhibition and stimulation of RCCT cell cyclic AMP (cAMP) production. Stimulation of cAMP accumulation occurred at analog concentrations of 0.1 μM to 100 μM with the rank order of potency NECA > PIA > CHA. Inhibition occurred at concentrations of 1 nM to 1 μM with the rank order of potency CHA > PIA > NECA. These effects on cAMP production were inhibited by 1,3-diethyl-8-phenylxanthine and isobutylmethylxanthine. CHA (50 nM) blunted AVP- and isoproterenol-stimulated cAMP accumulation. This modulation of hormone-induced cAMP production was abolished by pretreatment of RCCT cells with pertussis toxin. Prostaglandin E2 production was unaffected by 0.1 mM CHA. These findings indicate the presence of both inhibitory (A1) and stimulatory (A2) receptors for adenosine in RCCT cells. Moreover, occupancy of the A1 receptor causes inhibition of both basal and hormone-stimulated cAMP formation through an action on the inhibitory guanine nucleotide-binding regulatory component, N(i), of the adenylate cyclase system.

Original languageEnglish (US)
Pages (from-to)710-714
Number of pages5
JournalJournal of Clinical Investigation
Volume79
Issue number3
DOIs
StatePublished - Jan 1 1987

ASJC Scopus subject areas

  • Medicine(all)

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