PGE2 enhances cytokine-elicited nitric oxide production in mouse cortical collecting duct cells.
It has been documented that arginine vasopressin (AVP) and prostaglandin E(2) (PGE(2)) regulate water reabsorption in renal tubular cells. The present study was attempted to delineate the downstream signaling of AVP and PGE(2) in a cortical collecting duct cell line (M-1 cell). Using RT-PCR, we detected mRNA for V2 and VACM-1 but not for V1a and AII/AVP receptors of AVP. Furthermore, neither AVP nor V2 receptor agonist and antagonist alter cellular cAMP. These together with unchanged cellular Ca(2+) by AVP suggested that AVP pathway was not operating in M-1 cells. All four classical PGE(2) receptors with EP3 and EP4 as the most prominent were detected in M-1 cells. PGE(2), 11-deoxy-PGE(1) (EP2 and EP4 agonist), and 17-phenyl-trinor-PGE(2) (EP1 agonist) increased cellular concentration of cAMP. There was no effect of PGE(2) or EP1 agonist on cellular Ca(2+). These findings provide evidence of the involvement of PGE(2) cascade in M-1 cells. M-1 cells were capable of synthesizing nitric oxide (NO). Although individual cytokines did not affect NO production, a mixture of tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma elevated NO concentration to 4.5-fold of the control. Addition of PGE(2) and db-cAMP to the cytokine mixture further increased NO production to 7.0- and 9.8-fold, respectively, of that seen in non-treated cells. PGE(2) or db-cAMP alone, however, had no effect on NO production. The results of the study led us to speculate that enhanced production of cAMP via PGE(2) signaling pathway in M-1 cells could either stimulate or attenuate water reabsorption in renal tubule. While an increase in cAMP alone may enhance water reabsorption, a concomitant increase in cAMP and cytokines may inhibit water reabsorption in renal tubule.
Huang
Chien-Ning
CN
Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung Shan Medical University, Number 110, Section 1, Chien-Kuo North Road, Taichung 40203, Taiwan, ROC.
Liu
Kai-Li
KL
Cheng
Chun-Hsu
CH
Lin
Yu-Sheng
YS
Lin
Min-Jon
MJ
Lin
Ting-Hui
TH
D000818:Animals; D001127:Arginine Vasopressin / Q000502:physiology; D001483:Base Sequence; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis; D016207:Cytokines / Q000494:pharmacology*; D015232:Dinoprostone / Q000502:physiology*; D015759:Ionomycin / Q000494:pharmacology; D007685:Kidney Tubules, Collecting / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D018078:Receptors, Prostaglandin E / Q000032:analysis / Q000235:genetics; D017483:Receptors, Vasopressin / Q000032:analysis / Q000235:genetics; D012076:Renal Agents / Q000494:pharmacology; D015398:Signal Transduction
D016207:Cytokines; D018078:Receptors, Prostaglandin E; D017483:Receptors, Vasopressin; D012076:Renal Agents; C034862:vasotocin receptor; D001127:Arginine Vasopressin; D009569:Nitric Oxide; D015759:Ionomycin; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D015232:Dinoprostone