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Serotonin (5-hydroxytryptamine; 5-HT) is involved in heart valve tissue fibrosis, pulmonary arterial fibrosis, and pulmonary hypertension. We aimed at characterizing the antiserotonergic properties of the ergot alkaloid derivative terguride [1,1-diethyl-3-(6-methyl-8α-ergolinyl)urea] by using functional receptor assays and valvular interstitial cell culture. Terguride showed no vasoconstrictor effect in porcine coronary arteries (5-HT(2A) receptor bioassay) and no relaxant effect in porcine pulmonary arteries (5-HT(2B) receptor bioassay). Terguride behaved as a potent antagonist at 5-HT(2A) receptors (noncompetitive antagonist parameter pD'₂ 9.43) and 5-HT(2B) receptors (apparent pA₂ 8.87). Metabolites of terguride (N″-monodeethylterguride and 6-norterguride) lacked agonism at both sites. N″-monodeethylterguride and 6-norterguride were surmountable antagonists at 5-HT(2A) receptors (pA₂ 7.82 and 7.85, respectively) and 5-HT(2B) receptors (pA₂ 7.30 and 7.11, respectively). Kinetic studies on the effects of terguride in pulmonary arteries showed that the rate to reach drug-receptor equilibrium for terguride was fast. Washout experiments showed that terguride easily disappeared from the receptor biophase. Pretreatment with terguride inhibited 5-HT-induced amplification of ADP-stimulated human platelet aggregation (IC₅₀ 16 nM). In porcine valvular interstitial cells, 5-HT-induced activation of extracellular signal-regulated kinase (ERK) 1/2, an initiator of cellular proliferation and activity, was blocked by terguride as shown by Western blotting. In these cells, the stimulatory effect of 5-HT on [³H]proline incorporation (index of extracellular matrix collagen) was blocked by terguride. Because of the inhibition of both 5-HT(2A) and 5-HT(2B) receptors, platelet aggregation, and cellular proliferation and activity (ERK1/2 phosphorylation and collagen production) terguride may have therapeutic potential in the treatment of fibrotic disorders.
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http://dx.doi.org/10.1124/jpet.111.187906 | DOI Listing |
J Clin Med
May 2023
Department of Endocrinology, "Carol Davila" University of Medicine and Pharmacy & "C.I. Parhon" National Institute of Endocrinology, 011683 Bucharest, Romania.
Our purpose is to provide new insights concerning the challenges of pituitary apoplexy in pregnancy (PAP) and the postpartum period (PAPP). This is a narrative review of the English literature using a PubMed search. The inclusion criteria were clinically relevant original studies (January 2012-December 2022).
View Article and Find Full Text PDFJ Neurol Surg A Cent Eur Neurosurg
July 2022
Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
Background: The World Health Organization (WHO) classification of tumors of the endocrine organs was revised in 2017. The term atypical adenoma is no longer recommended, and tumors with rapid growth, radiologic invasion, and high K-67 labeling index are defined as high-risk adenomas. In this article, we present the case of an aggressive pituitary adenoma not fulfilling the new high-risk criteria with extraordinary rapid progression after very long stable disease, and discuss the remaining problem of the new criteria in terms of a complicated balance between pathologic findings and clinical features.
View Article and Find Full Text PDFSchizophr Res
August 2020
Department of Mental Health, Hospital Universitari Parc Taulí, I3PT. Sabadell, Barcelona, Spain; Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Cerdanyola, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.
Can J Physiol Pharmacol
August 2020
Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, C.P.14330, Mexico City, Mexico.
In vitro studies have suggested that terguride blocks the contractile and relaxant responses produced by 5-hydroxytryptamine (5-HT) via 5-HT receptors. This study has now investigated terguride's blocking properties on central/peripheral 5-HT receptors in anaesthetized or pithed rats. Male Wistar anaesthetized/pithed rats were cannulated for recording blood pressure and heart rate and for i.
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