Kohan D E, Padilla E
Division of Nephrology, Veterans Affairs Medical Center, Salt Lake City, Utah.
Am J Physiol. 1992 Oct;263(4 Pt 2):F607-12. doi: 10.1152/ajprenal.1992.263.4.F607.
Endothelin-1 (ET-1) may be an important factor in the regulation of inner medullary collecting duct (IMCD) physiology. This segment of the nephron synthesizes ET-1, expresses endothelin receptors, and responds to exogenous ET-1 by reducing Na(+)-K(+)-ATPase activity and water transport. Taken together, these findings suggest an autocrine role for ET-1 in the regulation of IMCD function; however, because of the polarized nature of the IMCD, it is not known if ET-1 secretion, receptors, and receptor activation occur on the same side of the cell. To examine this question, rat IMCD cells were grown to confluence on semipermeable membranes. These cells exhibited polar morphology with high transepithelial electrical resistances. Immunoreactive ET-1 was secreted primarily into the basolateral side. Furthermore, 125I-ET-1 bound predominantly to the basolateral surface. Finally, ET-1 (10(-8) M) stimulated prostaglandin E2 production only when added to the basolateral side. These data indicate, therefore, that ET-1 is capable of autocrine regulation of IMCD cells and that this effect occurs predominantly on the basolateral side.
内皮素-1（ET-1）可能是调节髓质集合管（IMCD）生理功能的一个重要因素。肾单位的这一部分合成ET-1，表达内皮素受体，并通过降低钠钾ATP酶活性和水转运对外源性ET-1作出反应。综上所述，这些发现提示ET-1在调节IMCD功能中具有自分泌作用；然而，由于IMCD的极性特点，尚不清楚ET-1的分泌、受体及受体激活是否发生在细胞的同一侧。为研究这个问题，将大鼠IMCD细胞培养至在半透膜上汇合。这些细胞呈现出具有高跨上皮电阻的极性形态。免疫反应性ET-1主要分泌至基底外侧。此外，125I-ET-1主要结合于基底外侧表面。最后，仅当将ET-1（10^(-8) M）添加至基底外侧时，它才刺激前列腺素E2的产生。因此，这些数据表明，ET-1能够对IMCD细胞进行自分泌调节，且这种作用主要发生在基底外侧。
