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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Inhibition of small conductance K+ -channels attenuated melatonin-induced relaxation of serotonin-contracted rat gastric fundus.
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Inhibition of small conductance K+ -channels attenuated melatonin-induced relaxation of serotonin-contracted rat gastric fundus.

机译：抑制小电导K +通道减弱了褪黑素诱导的血清素收缩大鼠胃底松弛。

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The aim of this study was to investigate the effects of melatonin on rat gastric fundus smooth muscle. Melatonin (10(-4) to 10(-3) M) had no effect on the basal tone of gastric smooth muscle. After precontraction with carbachol (10(-6) M) or serotonin (10(-7) M), melatonin caused a concentration dependent inhibitory action. The half maximal effect on serotonin-induced contraction was found with 1.12 +/- 0.86 x 10(-5) M of melatonin. Increasing concentrations of melatonin (10(-5) to 10(-3) M) resulted in a right shift of the serotonin concentration response curve (10(-10) to 10(-5) M). This inhibitory effect of melatonin was partially blocked in the presence of apamin (10(-10) to 10(-7) M), a specific blocker of the small conductance calcium-dependent potassium channel, but not in the presence of other potassium channel blockers like charybdotoxin (10(-8) M), glibenclamide (l0(-5) M), or tetraethylammonium (ODQ, 10(-4) M). The inhibitory effect was not changed in the presence of the neuronal blocker tetrodotoxin (10(-6) M), the selective P2-receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (3 x 10(-5) M), the nitric-oxide synthase inhibitor N-nitro-L-arginine (3 x 10(-4) M), or the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one (10(-4) M), suggesting that neither the purinergic, nitrergic, nor guanylate cyclase pathways were involved. We further investigated inhibitory responses to electrical field stimulation (EFS) at different frequencies under non-adrenergic, non-cholinergic (NANC) conditions on a serotonin-induced contraction in the presence of melatonin (10)-5 to 10(-4) M). Melatonin significantly reduced these inhibitory NANC responses in higher (8-32 Hz), but not lower (05-4 Hz), frequencies (16 Hz without melatonin, 103 +/- 6.3%; melatonin 10(-5) M, 80.4 +/- 7.5%; melatonin 10(-4) M, 39.1 +/- 17.1%). Melatonin had no effect on contractile responses induced by EFS under basal tone. These results demonstrate that the inhibitory effect of melatonin in rat gastric fundus smooth muscle is apamin sensitive, but is not affected by other potassium channel blockers. This suggests that melatonin may be another transmitter candidate for the apamin sensitive responses within the gastrointestinal tract.
机译：这项研究的目的是研究褪黑激素对大鼠胃底平滑肌的影响。褪黑激素（10（-4）至10（-3）M）对胃平滑肌的基础音没有影响。在用卡巴胆碱（10（-6）M）或5-羟色胺（10（-7）M）预收缩后，褪黑激素引起浓度依赖性抑制作用。发现褪黑素对血清素诱导的收缩有最大的一半效果，其变化为1.12 +/- 0.86 x 10（-5）M。褪黑激素浓度增加（10（-5）至10（-3）M）导致血清素浓度响应曲线向右移动（10（-10）至10（-5）M）。褪黑激素的这种抑制作用在存在于小传导性钙依赖性钾通道的特异性阻断剂-apamin（10（-10）至10（-7）M）的存在下被部分阻断，但在其他钾通道的存在下则未被阻断阻断剂如charybdotoxin（10（-8）M），glibenclamide（10（-5）M）或四乙铵（ODQ，10（-4）M）。在存在神经元阻滞剂河豚毒素（10（-6）M），选择性P2受体拮抗剂吡ido醛磷酸盐-6-偶氮苯基2'，4'-二磺酸（3 x 10（-5） ）M），一氧化氮合酶抑制剂N-硝基-L-精氨酸（3 x 10（-4）M）或鸟苷酸环化酶抑制剂1H- [1,2,4]草二唑[4,3-a] -quinoxalin-1-one（10（-4）M），表明嘌呤能，硝酸能和鸟苷酸环化酶途径均未涉及。我们进一步研究了褪黑素（10）-5至10（-4）M存在下在非肾上腺素，非胆碱能（NANC）条件下5-羟色胺引起的收缩中不同频​​率对电场刺激（EFS）的抑制反应）。褪黑激素以较高的频率（8-32 Hz）但不降低（05-4 Hz）的频率（不含褪黑激素的16 Hz，103 +/- 6.3％;褪黑激素10（-5）M，80.4 + /-7.5％;褪黑激素10（-4）M，39.1 +/- 17.1％。褪黑素对基础语调下EFS引起的收缩反应没有影响。这些结果表明褪黑激素对大鼠胃底平滑肌的抑制作用是对谷氨酰胺敏感的，但不受其他钾通道阻滞剂的影响。这表明褪黑激素可能是胃肠道内对apapa敏感反应的另一种递质。

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