ATP released from perivascular nerves hyperpolarizes smooth muscle cells by releasing an endothelium-derived factor in hamster mesenteric arteries.
1. The interaction between perivascular nerves and endothelium was investigated by measuring the changes in smooth muscle membrane potentials using intracellular microelectrode techniques in hamster mesenteric thin (100-150 microm) and thick (300-350 microm) arteries. 2. In both arteries, nerve stimulation evoked excitatory junction potentials (EJPs) which were strongly inhibited by pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) (0.5-5 microM). This result indicated that the EJPs were induced by the activation of P2X receptors. 3. Transient hyperpolarizations were evoked by trains of pulses at 20 Hz in PPADS (5 microM)-pre-treated thin arteries, but not in the thick arteries. ATP (100 microM) applied to adventitial surfaces mimicked the hyperpolarizations. Both the ATP- and nerve stimulation-induced hyperpolarizations were blocked by cibacron blue F3GA (2-100 microM) and were also abolished after endothelium removal, indicating that the neurally released ATP evoked transient hyperpolarization through the activation of P2Y receptors located on the endothelium. 4. In endothelium-intact preparations, intimal application of uridine 5'-triphosphate (UTP 100 microM), a P2Y2-like receptor agonist, but not 2-methylthio ATP (7 microM), hyperpolarized the smooth muscle. The UTP-induced hyperpolarization was significantly inhibited by cibacron blue F3GA and was abolished after endothelium removal. 5. These results suggest that ATP released from the perivascular nerves may reach the endothelium and activate P2Y2-like receptors to induce the release of an endothelium-derived hyperpolarizing factor in thin arteries.
Thapaliya
S
S
Department of Pathogenetic Veterinary Science, The United Graduate School, Gifu University, Gifu 501-1193, Japan.
Matsuyama
H
H
Takewaki
T
T
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D006224:Cricetinae; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials; D008638:Mesenteric Arteries / Q000187:drug effects / Q000294:innervation* / Q000502:physiology*; D008647:Mesocricetus; D008839:Microelectrodes; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D058910:Purinergic P2 Receptor Agonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology; D013498:Suramin / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology
D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D014227:Triazines; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; C012842:Cibacron Blue F 3GA; D011732:Pyridoxal Phosphate; D013498:Suramin; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D019331:NG-Nitroarginine Methyl Ester; D011224:Prazosin; D007213:Indomethacin