Bradykinin inhibits cyclic AMP accumulation in D384-human astrocytoma cells via a calcium-dependent inhibition of adenylyl cyclase

Cell Signal. 1993 May;5(3):279-88. doi: 10.1016/0898-6568(93)90018-h.


Bradykinin causes a concentration-dependent, transient rise in intracellular Ca2+ and a sustained inhibition of forskolin-, dopamine- and 5'-N-ethyl-carboxamidoadenosine (NECA)-stimulated cAMP accumulation in D384 astrocytoma cells. Chelation of intracellular calcium abolished bradykinin's inhibitory effect on cAMP accumulation. Chelating extracellular Ca2+ did not block the initial, but eliminated the sustained inhibition of cAMP accumulation. Increasing Ca2+ influx by calcium ionophore A23187 caused a concentration-dependent inhibition of stimulated cAMP accumulation. A hydroquinone derivative 2,5-di(tert-butyl)-1,4-benzohydroquinone (tBuBHQ), which inhibits microsomal Ca2+ sequestration, did not mimic the effect of bradykinin, although it increased [Ca2+]i even more than A23187 did. The inhibitory effect of bradykinin was not mediated by Ca2+/CaM-dependent stimulation of phosphodiesterase (PDE). Forskolin-stimulated adenylyl cyclase activity was inhibited by Ca2+ (10(-7) to 10(-3) M), both in ethyleneglycol-bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) washed and native D384 plasma membranes. This effect was not altered by calmodulin (CaM) or CaM-antagonists. Bradykinin treatment, which attenuates cAMP accumulation in intact cells, did not do so in plasma membranes. These findings suggest that bradykinin-induced inhibition of cAMP formation in D384 cells requires mobilization of [Ca2+]i and subsequent entry of Ca2+ which directly interacts with a component of the adenylyl cyclase system.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Adenosine / analogs & derivatives
  • Adenosine / antagonists & inhibitors
  • Adenosine / pharmacology
  • Adenosine-5'-(N-ethylcarboxamide)
  • Adenylyl Cyclase Inhibitors*
  • Astrocytoma / metabolism*
  • Bradykinin / pharmacology*
  • Brain Neoplasms / metabolism*
  • Calcimycin / pharmacology
  • Calcium / physiology*
  • Calmodulin / metabolism
  • Colforsin / antagonists & inhibitors
  • Colforsin / pharmacology
  • Cyclic AMP / metabolism*
  • Dopamine / pharmacology
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Humans
  • Hydroquinones / pharmacology
  • Inositol 1,4,5-Trisphosphate / physiology
  • Neoplasm Proteins / antagonists & inhibitors*
  • Pyrrolidinones / pharmacology
  • Rolipram
  • Signal Transduction / drug effects
  • Tumor Cells, Cultured


  • Adenylyl Cyclase Inhibitors
  • Calmodulin
  • Hydroquinones
  • Neoplasm Proteins
  • Pyrrolidinones
  • 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
  • Colforsin
  • 2,5-di-tert-butylhydroquinone
  • Adenosine-5'-(N-ethylcarboxamide)
  • Calcimycin
  • Egtazic Acid
  • Inositol 1,4,5-Trisphosphate
  • Cyclic AMP
  • Rolipram
  • Adenosine
  • Bradykinin
  • Calcium
  • 1-Methyl-3-isobutylxanthine
  • Dopamine