title: Presynaptic BK type Ca(2+)-activated K(+) channels are involved in prostanoid TP receptor-mediated inhibition of noradrenaline release from the rat gastric sympathetic nerves.
abstract: Previously, we reported that prostanoid TP receptor mediates the inhibition of electrically evoked noradrenaline release from gastric sympathetic nerves in rats. Prostanoid TP receptor has been shown to activate phospholipase C (PLC), which catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate to inositol 1,4,5-triphosphate (IP(3)) and diacylglycerol; IP(3) triggers the release of Ca(2+) from intracellular stores and diacylglycerol activates protein kinase C. In the present study, therefore, we examined whether these PLC-mediated mechanisms are involved in the TP receptor-mediated inhibition of gastric noradrenaline release using an isolated, vascularly perfused rat stomach. U-46619 (9,11-dideoxy-9alpha,11alpha-methanoepoxy PGF(2alpha)) (a prostanoid TP receptor agonist)-induced inhibition of noradrenaline release from the stomach was reduced by U-73122 [1-[6-[[(17beta)-3-methoxyestra-1,3,5(10)-trien-17-yl]-amino]hexyl]-1H-pyrrole-2,5-dine] (a PLC inhibitor) and ET-18-OCH(3) (1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphorylcholine) (a phosphatidylinositol-specific PLC inhibitor), respectively. 2-APB (2-aminoethyldiphenyl borate) (a putative IP(3) receptor antagonist) also abolished the U-46619-induced inhibition of noradrenaline release, but Ro 31-8220 [2-{1-[3-(amidinothio)propyl]-1H-indol-3-yl}-3-(1-methylindol-3-yl)-maleimide] (a protein kinase C inhibitor) had no effect. Furthermore, a small dose of tetraethylammonium and charybdotoxin [blockers of BK type Ca(2+)-activated K(+) channel] abolished the U-46619-induced inhibition, but apamin (a blocker of SK-type Ca(2+)-activated K(+) channel) had no effect. These results suggest that BK type Ca(2+)-activated K(+) channels are involved in prostanoid TP receptor-mediated inhibition of electrically evoked noradrenaline release from the gastric sympathetic nerve terminals in rats.
authors: Department of Pharmacology, School of Medicine, Kochi University, Nankoku, Kochi 783-8505, Japan.
authors: Kumiko
authors: K
authors: Nakamura
authors: Kunihiko
authors: K
authors: Yokotani
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001896:Boron Compounds / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005753:Gastric Mucosa / Q000378:metabolism; D066298:In Vitro Techniques; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017482:Receptors, Thromboxane / Q000378:metabolism*; D013270:Stomach / Q000187:drug effects / Q000294:innervation*; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D013569:Synapses; D019789:Tetraethylammonium / Q000494:pharmacology
chemical_list: D001896:Boron Compounds; D004791:Enzyme Inhibitors; D051036:Large-Conductance Calcium-Activated Potassium Channels; D011453:Prostaglandins; D017482:Receptors, Thromboxane; D001030:Apamin; D019789:Tetraethylammonium; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C109986:2-aminoethoxydiphenyl borate; D009638:Norepinephrine