1 This study aimed to investigate the 5-hydroxytryptamine (5-HT) receptors mediating contraction of ring preparations isolated from human pulmonary arteries and veins. In functional studies, the responses to 5-HT, sumatriptan, ergotamine, serotonin-O-carboxymethyl-glycyl-tyrosinamide (SCMGT), a-methyl 5-HT (a-Me) and 2-methyl 5-HT (2-Me) were studied with WAY100635, GR127935, ritanserin, zacopride and SB204070 as antagonists. 2 All agonists produced concentration-dependent contractions of human pulmonary artery and vein preparations. The order of potency (7log EC 50 values) was ergotamine (6.88)45-HT (6.41)5SCMGT (6.20)=sumatriptan (6.19) 5a-Me (6.04) in the artery, and ergotamine (7.84)45-HT (6.96)4suma-triptan (6.60)=a-Me (6.56)4SCMGT (6.09) in the vein. The potency of each agonist, except for SCMGT, was greater in vein than in artery preparations. Contractile responses to 5-HT were similar in intact and endothelium-denuded preparations but responses to sumatriptan were enhanced in artery rings without endothelium. 3 GR127935 (1 nM to 0.5 mM) produced an unsurmountable antagonism of the response to 5-HT, sumatriptan, ergotamine and SCMGT. Ritanserin (1 nM to 1 mM) also reduced the maximum contractile responses to 5-HT, ergotamine and a-Me in artery and vein preparations without aecting those to sumatriptan and SCMGT. In endothelium-denuded preparations, surmountable antagonism of sumatriptan by GR127935 (in the presence of ritanserin) and of a-Me by ritanserin (in the presence of GR127935) allowed for the calculation of the apparent pK B values of GR127935 (9.17+0.11 in artery and 9.11+0.05 in vein) and ritanserin (8.82+0.09 in artery and 8.98+0.12 in vein). 4 WAY100635 (1 nM to 1 mM), zacopride (1 nM to 1 mM), or SB204070 (1 nM) did not signi®cantly alter the concentration-response curves for 5-HT, sumatriptan, ergotamine, SCMGT or 2-Me in human pulmonary artery or vein thus indicating that 5-HT 1A , 5-HT 3 and 5-HT 4 receptors are presumably not involved in the contractile response to these agonists. 5 Binding studies using selective radioligands for dierent 5-HT receptors could not detect the presence of 5-HT 1A receptor binding in human pulmonary blood vessels whereas the 5-HT 1B/1D radioligand [ 3 H]-5-CT signi®cantly labelled a population of speci®c binding sites in both vessel types. The presence of 5-HT 2A receptors could also be inferred from the level of binding of [ 3 H]-ketanserin to membranes obtained from human pulmonary vessels, although signi®cance could not be reached for arteries. 5-HT 4 speci®c receptor binding was scarce in veins and absent in the case of arteries. 6 These ®ndings indicate that the human pulmonary artery and vein have a mixed functional population of 5-HT 1B/1D and 5-HT 2A receptors mediating the contractile response to 5-HT which is consistent with results of the binding studies.

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractPrimary cilia are nonmotile sensory organelles found on the surface of almost all kidney tubule epithelial cells. Being exposed to the tubular lumen, primary cilia are thought to be chemo-and mechanosensors of luminal composition and flux, respectively. We hypothesized that, Na + transport and primary cilia exist in a sensory functional connection in mature renal tubule epithelial cells. Our results demonstrate that primary cilium length is reduced in mineralocorticoid receptor (MR) knockout (KO) mice in a cell autonomous manner along the aldosterone-sensitive distal nephron (ADSN) compared with wild type (as µm ± SEM; 3.1 ± 0.2 vs 4.0 ± 0.1). In mouse cortical collecting duct (mCCD) cl1 cells, which are a model of collecting duct (CD) principal cells, changes in Na + transport intensity were found to mediate primary cilium length in response to aldosterone (as µm ± SEM: control: 2.7 ± 0.9 vs aldosterone treated: 3.8 ± 0.8). Cilium length was positively correlated with the availability of IFT88, a major intraflagellar anterograde transport complex B component, which is stabilized in response to exposure to aldosterone treatment. This suggests that the abundance of IFT88 is a regulated, rate limiting factor in the elongation of primary cilia. As previously observed in vivo, aldosterone treatment increased cell volume of cultured CD principal cells. Knockdown of IFT88 prevents ciliogenesis and inhibits the adaptive increase in cell size that was observed in response to aldosterone treatment. In conclusion, our results reveal a functional connection between Na + transport, primary cilia, and cell size, which may play a key role in the morphological and functional adaptation of the CD to sustained changes in active Na + reabsorption due to variations in aldosterone secretion. K E Y W O R D Saldosterone, cell volume, collecting duct, primary cilium, sodium 2626 | KOMARYNETS ET Al.