Gelperin D, Mann D, del Valle J, Wiley J W
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor.
J Pharmacol Exp Ther. 1994 Oct;271(1):507-14.
We examined the effect of bradykinin (Bk) on cytosolic calcium ([Ca++]i) in cultured rat ileal myenteric neurons. The receptor subtype(s) and calcium pool(s), e.g., extracellular and/or intracellular calcium that mediate Bk's effect on [Ca++]i in myenteric neurons, have not been reported. Superfusion with Bk (10 nM) increased [Ca++]i by 96 +/- 10 nM over basal levels in approximately 80% of the neurons tested that were not affected by a Bk-1 receptor antagonist but were inhibited 72% by a Bk-2 receptor antagonist. The Bk-generated increase in [Ca++]i was reduced by 45% and 52% of control response in calcium-free buffer and indomethacin, respectively, supporting involvement of extracellular and intracellular pools of calcium and mediation, in part, by a prostaglandin-dependent pathway. Bk increased [Ca2++]i by 54 +/- 6 nM in calcium-free buffer that was indomethacin insensitive, suggesting that Bk stimulation of extracellular calcium influx was mediated by a prostaglandin-dependent pathway. Bk (1 microM) increased tissue prostaglandin E2 (PGE2) production by 62% over basal levels in isolated rat ileal myenteric ganglia. Finally, superfusion with PGE2 (10 microM) increased [Ca++]i by 105 +/- 16 nM over basal levels that were blocked in calcium-free buffer. In summary, our studies suggest that cultured rat ileal myenteric neurons express the Bk-2 receptor subtype that is coupled to mobilization of extracellular and intracellular pools of calcium. Bk stimulates influx of extracellular calcium via a prostaglandin-dependent pathway.
我们研究了缓激肽（Bk）对培养的大鼠回肠肌间神经元胞质钙（[Ca++]i）的影响。介导Bk对肌间神经元[Ca++]i作用的受体亚型和钙库，如细胞外和/或细胞内钙，尚未见报道。用Bk（10 nM）进行灌流，在约80%受试神经元中，[Ca++]i比基础水平升高了96±10 nM，这些神经元不受Bk-1受体拮抗剂影响，但被Bk-2受体拮抗剂抑制了72%。在无钙缓冲液和吲哚美辛中，Bk引起的[Ca++]i升高分别降低了对照反应的45%和52%，这支持了细胞外和细胞内钙库的参与以及部分由前列腺素依赖性途径介导。在对吲哚美辛不敏感的无钙缓冲液中，Bk使[Ca2++]i升高了54±6 nM，表明Bk刺激细胞外钙内流是由前列腺素依赖性途径介导的。在分离的大鼠回肠肌间神经节中，Bk（1 μM）使组织前列腺素E2（PGE2）生成量比基础水平增加了62%。最后，用PGE2（10 μM）进行灌流，[Ca++]i比基础水平升高了105±16 nM，这在无钙缓冲液中被阻断。总之，我们的研究表明，培养的大鼠回肠肌间神经元表达与细胞外和细胞内钙库动员偶联的Bk-2受体亚型。Bk通过前列腺素依赖性途径刺激细胞外钙内流。
