Pharmacological characterization of purinoceptor-mediated constriction of submucosal arterioles in guinea pig ileum.
Sympathetic nerve stimulation causes a constriction of submucosal arterioles that is mediated by ATP acting at P2 receptors. In the present study, we examined the P2 receptor subtype mediating this response. A computer-assisted video monitoring system measured drug-induced changes in arteriolar diameter (resting diameter approximately 40-80 microns) in pieces of submucosa in vitro. The rank-order potency for vasoconstriction caused by several ATP analogs was alpha,beta-methylene ATP (alpha,beta-MeATP) > beta,gamma-methylene ATP = 2-methylthioATP > ATP > ADP. Constrictions caused by alpha,beta-MeATP were competitively antagonized by suramin (KB = 3.2 microM) and were noncompetitively blocked by pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (KB = 0.5 microM). Norepinephrine-induced constrictions were not affected by suramin (100 microM) or by pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (3 microM). Extracellular solutions with 0 added calcium prevented constrictions caused by alpha,beta-MeATP (0.1-1.0 microM), but not those caused by norepinephrine (3 and 10 microM). Nifedipine (0.3 and 1 microM) reduced constrictions caused by 40 and 60 mM extracellular potassium chloride, but not those caused by alpha,beta MeATP. These data indicate that P2X receptors mediate constriction of submucosal arterioles. P2X-mediated vasoconstriction is dependent on extracellular calcium, but calcium entry through nifedipine-sensitive calcium channels does not contribute to P2X-mediated vasoconstriction.
Galligan
J J
JJ
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, USA.
Herring
A
A
Harpstead
T
T
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000098:blood supply / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000098:blood supply / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D058913:Purinergic Agonists; D058914:Purinergic Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D011983:Receptors, Purinergic / Q000502:physiology*; D013498:Suramin / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D058913:Purinergic Agonists; D058914:Purinergic Antagonists; D011983:Receptors, Purinergic; D014662:Vasoconstrictor Agents; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D013498:Suramin; D000255:Adenosine Triphosphate; D009543:Nifedipine; D002118:Calcium