title: An endothelium-dependent contraction in canine mesenteric artery caused by caffeine.
abstract: 1. We examined whether or not caffeine caused an endothelium-dependent contraction (EDC) in canine mesenteric artery and whether the endothelium-dependent contracting factors (EDCF) were arachidonic acid metabolites. 2. Caffeine (1, 3 and 10 mM) caused a transient contraction in endothelium-intact arterial strips. Removal of the endothelium significantly attenuated the caffeine (1 and 3 mM)-induced contraction. 3. Caffeine (1 mM)-induced EDC was not affected by quinacrine and manoalide (phospholipase A2 inhibitors), indomethacin and aspirin (cyclo-oxygenase inhibitors), ONO-3078 and S-1452 (thromboxane A2 antagonists) or AA-861 and TMK-777 (lipoxygenase inhibitors). 4. Caffeine (1 mM)-induced EDC was also unaffected by 50-235 (an endothelin A receptor antagonist). In addition, catalase combined treatment with superoxide dismutase, or allopurinol (antioxidant) did not affect the EDC. 5. Gro-PIP and NCDC (phospholipase C inhibitors) did not affect the caffeine-induced EDC. However, wortmannin (a phospholipase D inhibitor) and staurosporine (a protein kinase C inhibitor) attenuated the caffeine-induced EDC. 6. The present experiments demonstrate that caffeine causes an EDC in canine mesenteric artery and suggest that the EDCF mediating this response is probably not arachidonic acid metabolites, endothelin or superoxide. Instead, caffeine-induced EDC may be due to activation of the phospholipase D pathway.
authors.affiliation: Pharmacology Division, Kyoto University, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Jino
authors.forename: H
authors.initials: H
authors.lastname: Usui
authors.forename: S
authors.initials: S
authors.lastname: Temma
authors.forename: H
authors.initials: H
authors.lastname: Shirahase
authors.forename: K
authors.initials: K
authors.lastname: Kurahashi
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000502:physiology; D001488:Basilar Artery / Q000187:drug effects; D002110:Caffeine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004285:Dogs; D016232:Endothelins / Q000494:pharmacology / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010739:Phospholipase D / Q000037:antagonists & inhibitors; D013481:Superoxides / Q000378:metabolism; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
chemical_list: D016861:Cyclooxygenase Inhibitors; D016232:Endothelins; D016859:Lipoxygenase Inhibitors; D013481:Superoxides; D016718:Arachidonic Acid; D002110:Caffeine; D013928:Thromboxane A2; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D010739:Phospholipase D