Cyclic adenosine monophosphate-dependent vascular responses to purinergic agonists adenosine triphosphate and uridine triphosphate in the anesthetized mouse.
The mechanism by which purinergic agonist adenosine triphosphate (ATP) and uridine triphosphate (UTP) decrease systemic arterial pressure in the anesthetized mouse was investigated. Intravenous injections of adenosine triphosphate (ATP) and uridine triphosphate (UTP) produced dose-dependent decreases in systemic blood pressure in the mouse. The order of potency was ATP > UTP. Vasodilator responses to ATP and UTP were altered by the cyclic adenosine monophosphate (cAMP) phosphodiesterase inhibitor rolipram. The vascular responses to ATP and UTP were not altered by a nitric oxide synthase inhibitor, a cyclooxygenase inhibitor, a cGMP phosphodiesterase inhibitor, or a particular P2 receptor antagonist. These data suggest that ATP and UTP cause a decrease in systemic arterial pressure in the mouse via a cAMP-dependent pathway via a novel P2 receptor linked to adenylate cyclase and that nitric oxide release, prostaglandin synthesis, cGMP, and P2X1, P2Y1, and P2Y4 receptors play little or no role in the vascular effects of these purinergic agonists in the mouse.
Shah
Mrugeshkumar K
MK
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana, USA. Mrugshah@hotmail.com
Kadowitz
Philip J
PJ
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism* / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008469:Meclofenamic Acid / Q000494:pharmacology; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D058919:Purinergic P2 Receptor Antagonists; D011688:Purinones / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D020889:Rolipram / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D010726:Phosphodiesterase Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D011688:Purinones; D018048:Receptors, Purinergic P2; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D009569:Nitric Oxide; D008469:Meclofenamic Acid; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D015106:3',5'-Cyclic-GMP Phosphodiesterases; C011145:zaprinast; D020889:Rolipram; D014544:Uridine Triphosphate; D019331:NG-Nitroarginine Methyl Ester