Endogenous extracellular purine nucleotides redirect alpha2-adrenoceptor signaling.
Many receptors coupled to inhibitory Go/Gi-type G proteins often also produce stimulatory signals like Ca2+ mobilisation. When expressed in CHO cells the alpha2-adrenoceptor subtypes alpha2A, alpha2B and alpkha2C mobilised Ca2+. These responses were strongly reduced by the P2Y-purinoceptor antagonist suramin. A large proportion of the total pool of purine nucleotides was found extracellularly. Removal of extracellular nucleotides with apyrase or by constant perfusion had a similar effect as suramin. These treatments did not affect the alpha2-adrenoceptor-mediated inhibition of cAMP production. This indicates that cells may be primed or their signaling pathways redirected towards Ca2+ mobilisation by 'autocrine' release of nucleotides.
Department of Physiology, Uppsala University, BMC, Sweden. karl.akerman@fysiologi.uu.se
K E
KE
Akerman
J
J
Näsman
P E
PE
Lund
R
R
Shariatmadari
J P
JP
Kukkonen
D000255:Adenosine Triphosphate / Q000494:pharmacology* / Q000502:physiology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001081:Apyrase / Q000494:pharmacology; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D058919:Purinergic P2 Receptor Antagonists; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013498:Suramin / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D004791:Enzyme Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D018341:Receptors, Adrenergic, alpha-2; D013498:Suramin; D019284:Thapsigargin; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D001081:Apyrase; D000252:Calcium-Transporting ATPases; D002118:Calcium; D009638:Norepinephrine