5-羟色胺和多巴胺对负鼠肾细胞中钠-磷酸盐共转运体的相反旁分泌作用。

Opposite paracrine effects of 5-HT and dopamine on Na(+)-Pi cotransport in opossum kidney cells.

作者信息

de Toledo F G, Beers K W, Berndt T J, Thompson M A, Tyce G M, Knox F G, Dousa T P

机构信息

Department of Physiology, Mayo Clinic and Foundation, Rochester, Minnesota, USA.

出版信息

Kidney Int. 1997 Jul;52(1):152-6. doi: 10.1038/ki.1997.314.

DOI:10.1038/ki.1997.314

PMID:9211357

Abstract

Serotonin (5-HT) was recently reported to inhibit cAMP generation in oppossum (OK) cells. We thus investigated the effects of 5-HT upon the Na(+)-Pi cotransport in cultured OK cells and its interactions with dopamine. Incubation of OK cells with 1 nM-10 microM 5-HT resulted in dose-dependent stimulation of Na(+)-Pi contransport (ED50 approximately equal to 8 nM) and also counteracted inhibition of Na(+)-Pi cotransport elicited by dopamine. Pre-incubation with 5-HT decreased cAMP accumulation elicited by forskolin or dopamine and pre-treatment with pertussis toxin abolished both the inhibitory effect of 5-HT upon cAMP levels and stimulation of Na(+)-Pi cotransport. Incubation of OK cells with the 5-HT precursor 5-hydroxytryptophan resulted in time- and dose-dependent accumulation of 5-HT in the medium that also elicited an increase in Na(+)-Pi cotransport. Both the effects of 5-HT and dopamine on Na(+)-Pi cotransport were prevented by carbidopa. The stimulatory effect of 5-HT was specific for the Na(+)-Pi cotransport system since no effects were observed on Na(+)-alanine cotransport. The results indicate that 5-HT stimulates Na(+)-Pi cotransport at least in part via inhibition of cAMP accumulation. We propose that 5-HT and dopamine have opposite actions as paracrine/autocrine regulators of Na(+)-Pi cotransport via opposite effects upon cAMP formation.

摘要

最近有报道称，血清素（5-羟色胺，5-HT）可抑制负鼠（OK）细胞中cAMP的生成。因此，我们研究了5-HT对培养的OK细胞中Na(+)-Pi共转运的影响及其与多巴胺的相互作用。用1 nM - 10 μM的5-HT孵育OK细胞会导致Na(+)-Pi共转运呈剂量依赖性刺激（半数有效剂量约等于8 nM），并且还能抵消多巴胺对Na(+)-Pi共转运的抑制作用。用5-HT预孵育可降低福斯高林或多巴胺引起的cAMP积累，用百日咳毒素预处理可消除5-HT对cAMP水平的抑制作用以及对Na(+)-Pi共转运的刺激作用。用5-HT前体5-羟色氨酸孵育OK细胞会导致培养基中5-HT随时间和剂量依赖性积累，这也会引起Na(+)-Pi共转运增加。卡比多巴可阻止5-HT和多巴胺对Na(+)-Pi共转运的作用。5-HT的刺激作用对Na(+)-Pi共转运系统具有特异性，因为对Na(+)-丙氨酸共转运未观察到影响。结果表明，5-HT至少部分通过抑制cAMP积累来刺激Na(+)-Pi共转运。我们提出，5-HT和多巴胺作为Na(+)-Pi共转运的旁分泌/自分泌调节因子，通过对cAMP形成的相反作用而具有相反的作用。