Endothelins in Canine Genitourinary Tissues

Langenstroer, Peter; Tang, Rui; Divish, Barbara J.; Opgenorth, Terry J.; Shapiro, Ellen; Lepor, Herbert

doi:10.1097/00005392-199703000-00103

Cited by 5 publications

(11 citation statements)

References 15 publications

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“…Indeed, the present study demonstrated that both ET A and ET B are present in the epithelial cells of the human urinary bladder. These findings are in line with previous reports that ET A and ET B are expressed along the lower genitourinary tract [34,42,43] . It would be of interest to compare urinary ET receptor excretion between normotensive and hypertensive subjects, an approach that could be of value in exploring the pathophysiology of hypertension and salt sensitivity.…”

Section: Discussionsupporting

confidence: 93%

Urinary Excretion of Endothelin Receptors ETA and ETB in Hypertensive Patients and Normotensive Subjects

Karram¹,

Khamaisi²,

Bishara³

et al. 2009

Kidney Blood Press Res

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Background/Aims: Endothelin (ET)-1 is produced by most renal cell types. Renal tubular and vascular cells express both the ET receptors ET_A and ET_B. Since significant amounts of ET-1 of renal origin were detected in human urine, urinary ET-1 has been used as an index for the capacity of renal ET-1 production. Here, we determine the existence of additional components of the intrarenal ET system, namely the ET_A and ET_B receptor subtypes, in the urine of normal and hypertensive subjects. Methods: ET_A and ET_B receptors were detected in urine samples that were concentrated by TCA precipitation, Speedvac or ProteoSpin™. Results: Analysis of the human urine extracts revealed the existence of approximately 50 and 55 kDa of immunoreactive proteins, corresponding to ET_B and ET_A, respectively, indicating that intact ET_A and ET_B are excreted in the urine of healthy subjects and hypertensive patients. Normotensive and hypertensive subjects had statistically comparable ET_B excretion normalized to creatinine (0.58 ± 0.16 vs. 0.83 ± 0.17 μg/mg creatinine, respectively; p = 0.304). In contrast, ET_A excretion was higher among hypertensive subjects (0.05 ± 0.01 vs. 0.11 ± 0.02 μg/mg creatinine; p = 0.0451). Immunostaining of ET_A and ET_B in the human urinary system revealed expression of both receptors, principally in tubular cells (mainly in medullary collecting ducts) and in the bladder urothelium, and ET_A expression in the peritubular capillaries and arterioles. Urinary ET receptors closely and inversely correlated with indices of urine concentration, suggesting that their shedding is principally affected by urine flow. Conclusion: ET receptors are present in human urine, conceivably originating within the urinary system. Their excretion is principally affected by urinary concentration. It remains to be determined whether urinary ET_A/ET_B is of physiological/pathophysiological relevance.

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Section: Discussionsupporting

confidence: 93%

Urinary Excretion of Endothelin Receptors ETA and ETB in Hypertensive Patients and Normotensive Subjects

Karram¹,

Khamaisi²,

Bishara³

et al. 2009

Kidney Blood Press Res

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“…The present study indicates that, in keeping with previous findings in vivo, expression of the ET-1 gene in vitro is primarily an epithelial phenomenon (5). In contrast, attempts to amplify ET-1 sequences from stromal cell RNA by RT-PCR failed to produce a detectable signal.…”

Section: Discussionsupporting

confidence: 90%

“…Previous studies in the prostate suggest that ET-1-like immunoreactivity is associated primarily with the glandular epithelium, with ET A and ET B receptors predominating in the stromal and glandular components, respectively (5,10). Previous studies in the prostate suggest that ET-1-like immunoreactivity is associated primarily with the glandular epithelium, with ET A and ET B receptors predominating in the stromal and glandular components, respectively (5,10).…”

mentioning

confidence: 98%

“…(J Clin Endocrinol Metab 82: 508 -513, 1997) T HE ENDOTHELIN (ET) family comprises three structurally related peptides, ET-1, ET-2, and ET-3 (potentially derived from a common ancestral gene), whose primary action is as potent vasoconstrictors but which display a multitude of functions in a diverse array of tissues (1)(2)(3)(4)(5). Competitive binding studies demonstrate a single class of binding site in both primary benign epithelia (dissociation constant ϭ 1.85 ϫ 10 Ϫ10 mol/L; maximal binding capacity ϭ 2.7 ϫ 10 4 binding sites/cell), and stroma (dissociation constant ϭ 1.93 ϫ 10 Ϫ10 mol/L; maximal binding capacity ϭ 3.7 ϫ 10 5 binding sites/cell).…”

mentioning

confidence: 99%

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In VitroExpression of Endothelin-1 (ET-1) and the ET_Aand ET_BET Receptors by the Prostatic Epithelium and Stroma¹

Grant¹,

Brown²,

Roach³

et al. 1997

The Journal of Clinical Endocrinology & Metabolism

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RT-PCR analysis of total RNA prepared from the prostate cancer cell lines DU145 and PC3 and from primary epithelial cells indicated the presence of endothelin-1 (ET-1) messenger RNA (mRNA). Neither the LNCaP cell line nor primary prostatic stromal cells possess ET-1 mRNA transcripts. Seventy-two-hour-conditioned media derived from DU145, PC3, and primary epithelia contain immunoreactive ET concentrations equivalent to 0.814 +/- 0.048, 0.330 +/- 0.050, and 0.856 +/- 0.055 fmol/mL/10(6) cells after 72 h, respectively. Basal immunoreactive ET secretion was exhibited by LNCaP (0.029 +/- 0.009 fmol/mL/10(6) cells after 72 h) and stromal cells (0.067 +/- 0.007 fmol/ mL/10(6) cells after 72 h). Examination of ETA and ETB gene expression by RT-PCR demonstrates that ET receptor mRNA is almost completely undetectable in the prostate cancer cell lines. Both ETA and ETB mRNAs are detectable in primary cultures of prostatic epithelia and stroma. Competitive binding studies demonstrate a single class of binding site in both primary benign epithelia (dissociation constant = 1.85 x 10(-10) mol/L; maximal binding capacity = 2.7 x 10(4) binding sites/cell), and stroma (dissociation constant = 1.93 x 10(-10) mol/L; maximal binding capacity = 3.7 x 10(5) binding sites/cell). Use of selective ET receptor antagonists confirmed that the predominant stromal receptor subtype expressed in vitro is ETB. This receptor seems not to be coupled to mitogenic pathways because no growth response to exogenous ET-1 or cooperation between ET-1 and bFGF could be observed. Similarly, no effect of ET-1 or the ET-converting enzyme inhibitor, phosphoramidon, on benign epithelial cells could be observed over a 4-day period.

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“…In addition to their effects on vascular smooth muscles, ETs cause contractile responses in the trachea [5][6][7], bronchus [8], and uterus [9], positive inotropic and chronotropic effects on the myocardium [10], and are mitogenic for cultured smooth muscle cells [11][12][13] and fibroblasts [14]. ETs produce prolonged contractile responses in isolated urinary tract smooth muscles from rabbits [15][16][17] and humans [8], and cause rhythmic contractions of the rabbit pelvis [18]. regional distributions of autonomic and calcium antagonist receptors in the urinary tract correlate well with physiological functions [25,26], we investigated the functional (pharmacological) and biochemical properties of ET receptors in the proximal, middle and distal rabbit prostatic urethra.…”

Section: Introductionmentioning

confidence: 99%

Regional differences in the functional and biochemical properties of endothelin receptor subtypes in the rabbit prostatic urethra

et al. 2007

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OBJECTIVE To examine the regional differences in the functional (pharmacological) and biochemical properties of endothelin (ET) receptors in the rabbit prostatic urethra. MATERIALS AND METHODS The properties of ET receptors in 6‐month‐old male rabbit prostatic urethras were examined using isolated muscle‐bath and radioligand receptor‐binding techniques. Using plasma membrane suspensions, saturation and inhibition experiments with [125I]ET‐1 and unlabelled agonists and antagonists (ETA‐selective antagonist BQ123, and ETB‐selective agonist sarafotoxin 6c, STX6c) were done to determine the ET receptor densities and their subtype specificities in the different regions of the urethra. RESULTS The ETs (ET‐1 and ET‐3) produced significant concentration‐dependent contractile responses in the smooth muscle strips from the different regions of the urethra. Although the maximum contractile responses induced by ET‐1 were similar in the different regions, the maximum contractile responses induced by ET‐3 were greater in the distal region than in the proximal or middle regions, suggesting that the contractile response to ET‐1 is more potent than that to ET‐3 in all regions, and that there are region‐specific differences in the responses to ET‐3 but not ET‐1. Moreover, the ET‐3‐induced contractile response was suppressed by BQ788 (a selective antagonist of the ETB receptor) suggesting that the ETB receptor subtype contributes to the contractile responses mediated by ET‐3. The ET receptors were expressed in higher concentrations in the distal than in the proximal or middle regions. BQ123 and STX6c inhibited [125I]ET‐1 binding in all regions with high and low affinity constants, indicating the presence of both ETA and ETB receptor subtypes. The proportions of high‐affinity binding sites for BQ123, representing ETA receptors, were ≈ 68%, 63% and 42% in the proximal, middle and distal regions, respectively. By contrast, the proportions of high‐affinity binding sites for STX6c, representing ETB receptors, were ≈ 27%, 35% and 52% in the proximal, middle, and distal regions, respectively. These data indicate the presence of regional differences in the densities and subtype specificities of ET receptor subtypes, and the existence of regional differences in the rabbit prostatic urethra. CONCLUSION The results suggest regional differences in ETB receptor subtypes that mediate contractile responses to ET‐3, reflecting differences in the densities and specificities of the ET receptor subtypes in the rabbit prostatic urethra.

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Endothelins in Canine Genitourinary Tissues

Cited by 5 publications

References 15 publications

Urinary Excretion of Endothelin Receptors ET<sub>A</sub> and ET<sub>B</sub> in Hypertensive Patients and Normotensive Subjects

Urinary Excretion of Endothelin Receptors ET<sub>A</sub> and ET<sub>B</sub> in Hypertensive Patients and Normotensive Subjects

In VitroExpression of Endothelin-1 (ET-1) and the ET_Aand ET_BET Receptors by the Prostatic Epithelium and Stroma¹

Regional differences in the functional and biochemical properties of endothelin receptor subtypes in the rabbit prostatic urethra

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Endothelins in Canine Genitourinary Tissues

Cited by 5 publications

References 15 publications

Urinary Excretion of Endothelin Receptors ET<sub>A</sub> and ET<sub>B</sub> in Hypertensive Patients and Normotensive Subjects

Urinary Excretion of Endothelin Receptors ET<sub>A</sub> and ET<sub>B</sub> in Hypertensive Patients and Normotensive Subjects

In VitroExpression of Endothelin-1 (ET-1) and the ETAand ETBET Receptors by the Prostatic Epithelium and Stroma1

Regional differences in the functional and biochemical properties of endothelin receptor subtypes in the rabbit prostatic urethra

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Product

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In VitroExpression of Endothelin-1 (ET-1) and the ET_Aand ET_BET Receptors by the Prostatic Epithelium and Stroma¹