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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

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

Kumiko Nakamura, Kunihiko Yokotani

Eur J Pharmacol. 2010 Mar 10;629(1-3):111-7.

PMID: 19961846

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4244391	1-O-Octadecyl-2-O-methyl-sn-glycero-3-phosphorylcholine			Price

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