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Pericardial mesothelial cells produce endothelin-1 and possess functional endothelin ETB receptors.
Eur J Pharmacol. 1998 Apr 24; 347(2-3):329-35.EJ

Abstract

We investigated the endothelin production and endothelin receptor activity of pericardial mesothelial cells obtained from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. The pericardial mesothelial cells were maintained in vitro and the production of endothelin-1 by these cells was evaluated by using a sensitive sandwich-type enzyme immunoassay for endothelin-1 and big endothelin-1. Endothelin receptor subtypes were pharmacologically analyzed by measuring the changes of intracellular Ca2+ concentration ([Ca2+]i) in pericardial mesothelial cells. Mesothelial cells from both strains produced more immunoreactive endothelin-1 than big endothelin-1. The production of immunoreactive endothelin-1 progressively increased in a culture time-dependent manner. The amount of immunoreactive endothelin-1 detected after 72 h in pericardial mesothelial cells of SHR was significantly (P < 0.05) higher than that in the cells of WKY rats (SHR: 196.7 +/- 19.1 pg/10(6) cells; WKY: 122.7 +/- 10.6 pg/10(6) cells). Endothelin-1 and endothelin-3 induced elevation of [Ca2+]i in pericardial mesothelial cells. The selective agonist of the endothelin ETB receptor, sarafotoxin S6c, also induced elevation of [Ca2+]i. The endothelin- and sarafotoxin S6c-induced elevations of [Ca2+]i in pericardial mesothelial cells from SHR were greater than those in mesothelial cells from WKY rats. The endothelin ETB receptor antagonist, IRL 1038 ([Cys11,Cys15]endothelin-1-(11-21)), significantly inhibited the endothelin-1- and endothelin-3-induced changes in [Ca2+]i. The endothelin ETA receptor antagonist, FR 1393171 ((R)2-[(R)-2-[(S)-2-[[1-(hexahydro-1H-azepinyl)]carbonyl]ammino -4-methylpentanoyl]amino-3-[3-(1-methyl-1H-indoyl)]propio nyl]amino-3-(2-pyridyl)propionic acid), did not affect these changes. From these results, pericardial mesothelial cells from both SHR and WKY rats shared the ability to produce endothelin-1 spontaneously in culture, although consistently greater production was detected in cultures of SHR origin. Moreover, pericardial mesothelial cells of SHR origin may have increased numbers of endothelin ETB receptors and/or a more active signal transduction system compared with those of WKY rats. These results suggest that endothelin-1 may play an important role in the pericardium in an autocrine and/or paracrine fashion.

Authors+Show Affiliations

Department of Comparative Pathophysiology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Japan. akuwam@hongo.ecc.u-tokyo.ac.jpNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9653900

Citation

Kuwahara, M, and M Kuwahara. "Pericardial Mesothelial Cells Produce Endothelin-1 and Possess Functional Endothelin ETB Receptors." European Journal of Pharmacology, vol. 347, no. 2-3, 1998, pp. 329-35.
Kuwahara M, Kuwahara M. Pericardial mesothelial cells produce endothelin-1 and possess functional endothelin ETB receptors. Eur J Pharmacol. 1998;347(2-3):329-35.
Kuwahara, M., & Kuwahara, M. (1998). Pericardial mesothelial cells produce endothelin-1 and possess functional endothelin ETB receptors. European Journal of Pharmacology, 347(2-3), 329-35.
Kuwahara M, Kuwahara M. Pericardial Mesothelial Cells Produce Endothelin-1 and Possess Functional Endothelin ETB Receptors. Eur J Pharmacol. 1998 Apr 24;347(2-3):329-35. PubMed PMID: 9653900.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pericardial mesothelial cells produce endothelin-1 and possess functional endothelin ETB receptors. AU - Kuwahara,M, AU - Kuwahara,M, PY - 1998/7/8/pubmed PY - 1998/7/8/medline PY - 1998/7/8/entrez SP - 329 EP - 35 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 347 IS - 2-3 N2 - We investigated the endothelin production and endothelin receptor activity of pericardial mesothelial cells obtained from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. The pericardial mesothelial cells were maintained in vitro and the production of endothelin-1 by these cells was evaluated by using a sensitive sandwich-type enzyme immunoassay for endothelin-1 and big endothelin-1. Endothelin receptor subtypes were pharmacologically analyzed by measuring the changes of intracellular Ca2+ concentration ([Ca2+]i) in pericardial mesothelial cells. Mesothelial cells from both strains produced more immunoreactive endothelin-1 than big endothelin-1. The production of immunoreactive endothelin-1 progressively increased in a culture time-dependent manner. The amount of immunoreactive endothelin-1 detected after 72 h in pericardial mesothelial cells of SHR was significantly (P < 0.05) higher than that in the cells of WKY rats (SHR: 196.7 +/- 19.1 pg/10(6) cells; WKY: 122.7 +/- 10.6 pg/10(6) cells). Endothelin-1 and endothelin-3 induced elevation of [Ca2+]i in pericardial mesothelial cells. The selective agonist of the endothelin ETB receptor, sarafotoxin S6c, also induced elevation of [Ca2+]i. The endothelin- and sarafotoxin S6c-induced elevations of [Ca2+]i in pericardial mesothelial cells from SHR were greater than those in mesothelial cells from WKY rats. The endothelin ETB receptor antagonist, IRL 1038 ([Cys11,Cys15]endothelin-1-(11-21)), significantly inhibited the endothelin-1- and endothelin-3-induced changes in [Ca2+]i. The endothelin ETA receptor antagonist, FR 1393171 ((R)2-[(R)-2-[(S)-2-[[1-(hexahydro-1H-azepinyl)]carbonyl]ammino -4-methylpentanoyl]amino-3-[3-(1-methyl-1H-indoyl)]propio nyl]amino-3-(2-pyridyl)propionic acid), did not affect these changes. From these results, pericardial mesothelial cells from both SHR and WKY rats shared the ability to produce endothelin-1 spontaneously in culture, although consistently greater production was detected in cultures of SHR origin. Moreover, pericardial mesothelial cells of SHR origin may have increased numbers of endothelin ETB receptors and/or a more active signal transduction system compared with those of WKY rats. These results suggest that endothelin-1 may play an important role in the pericardium in an autocrine and/or paracrine fashion. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/9653900/Pericardial_mesothelial_cells_produce_endothelin_1_and_possess_functional_endothelin_ETB_receptors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(98)00110-1 DB - PRIME DP - Unbound Medicine ER -