An endothelium-derived factor modulates purinergic neurotransmission to mesenteric arterial smooth muscle of hamster.
The interaction between the endothelium and purinergic perivascular nerves was investigated by measuring the changes in amplitude of excitatory junction potential (EJP) of smooth muscle cells in hamster mesenteric arteries (100-350 microm). Uridin-5'-triphosphate (UTP) (100 microM) applied to endothelium-intact preparations evoked a hyperpolarization of 17.0 +/- 0.7 mV (n=46). During this hyperpolarization, the amplitude of electrically evoked EJPs was inhibited to about 50% of that of the control. In endothelium-denuded preparations, UTP (100 microM) neither hyperpolarized the smooth muscle nor inhibited the amplitude of the EJP. Neither a nitric oxide (NO) synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME) (100 microM), nor a cyclooxygenase inhibitor, indomethacin (1 microM), had an effect on the UTP-evoked hyperpolarization and inhibition of the electrically evoked EJP. The UTP-evoked membrane hyperpolarization and inhibition of the EJP amplitude was antagonized by the P2Y receptor antagonist, cibacron blue (100 microM). Endothelium-derived hyperpolarizing factor (EDHF)-mediated hyperpolarization was inhibited by either adventitial or intimal application of apamin (0.1 micro and charybdotoxin (0.1 microM). However, the EJP inhibition was still present. In apamin- and charybdotoxin-treated preparations, focal application of adenosine 5'-triphosphate (ATP) (10 mM) evoked a depolarization of 15.5 +/- 1.3 mV (n=15). This postjunctional response was not modified by UTP (15.3 +/- 1.7 mV, n=4, P>0.05). These results suggest that exogenously applied UTP activates P2Y receptors of endothelium to release endothelium-derived factors, which in turn inhibit ATP release from purinergic nerves.
Thapaliya
Sharada
S
Department of Pathogenetic Veterinary Science, The United Graduate School, Gifu University, Yanagido 1-1, Gifu 501-1193, Japan.
Matsuyama
Hayato
H
El-Mahmoudy
AbuBakr
A
Shimizu
Yasutake
Y
Takewaki
Tadashi
T
D015761:4-Aminopyridine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001685:Biological Factors / Q000502:physiology*; D018999:Charybdotoxin / Q000494:pharmacology; D006224:Cricetinae; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000294:innervation / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D008647:Mesocricetus; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010042:Ouabain / Q000494:pharmacology; D020110:Pinacidil / Q000494:pharmacology; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D019789:Tetraethylammonium / Q000494:pharmacology; D013997:Time Factors; D014227:Triazines / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D001685:Biological Factors; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D014227:Triazines; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D018999:Charybdotoxin; D001030:Apamin; D009569:Nitric Oxide; C047008:17-octadecynoic acid; D010042:Ouabain; C012842:Cibacron Blue F 3GA; D019789:Tetraethylammonium; D020110:Pinacidil; D000255:Adenosine Triphosphate; D015761:4-Aminopyridine; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D005905:Glyburide; D014544:Uridine Triphosphate; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin