Involvement of ObRb receptor, nitric oxide, and BK Ca channel signaling pathways in leptin-induced relaxation of pregnant mouse uterus.

Autor: Kishor Kumar DG; Division of Pharmacology and Toxicology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India, 243122., Pashupathi M; Division of Animal Biochemistry, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India, 243122., Vaidhya A; Division of Pharmacology and Toxicology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India, 243122., Ravi Prakash G; Division of Pharmacology and Toxicology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India, 243122., Bramhane A; Division of Physiology and Climatology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India, 243122., Panigrahi M; Division of Animal Genetics and Breeding, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India, 243122., Karikalan M; Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India, 243122., Lingaraju MC; Division of Pharmacology and Toxicology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India, 243122., Manickam K; Division of Pharmacology and Toxicology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India, 243122., Singh TU; Division of Pharmacology and Toxicology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India, 243122., Parida S; Division of Pharmacology and Toxicology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India, 243122. Electronic address: subhaparida1210@gmail.com.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2024 Sep 05; Vol. 978, pp. 176796. Date of Electronic Publication: 2024 Jun 28.
DOI: 10.1016/j.ejphar.2024.176796
Abstrakt: The purpose of this study was to determine the receptor subtype and the underlying mechanisms involved in the relaxant effect to leptin in mid- and late-pregnant mouse uterus. We determined the relative mRNA expression of receptor subtypes, eNOS, and BK Ca channel by quantitative PCR and also the overall receptor expression by immunohistochemistry. Isometric tension studies were conducted to evaluate the effects of leptin and to delineate its mechanisms. A selective siRNA for the ObRb receptor was used to determine the participation of the receptor subtype in biochemical and molecular effects of leptin. The relaxant response to leptin was greater in mid-pregnancy compared to late pregnancy and was mediated by the activation of BK Ca channels by eNOS-derived nitric oxide in an ObRb receptor-dependent manner. In comparison to mid-pregnancy, expression of short forms (mainly ObRa receptor) of the receptor was significantly increased in late pregnancy, whereas ObRb receptor expression was similar in both phases. The results of the study suggest that ObRb receptor mediates leptin-induced increase in eNOS expression and NO synthesis. Leptin-induced eNOS expression and activation cause cGMP-independent stimulation of BK Ca channels causing uterine relaxation. Increased short forms of the receptors and reduced BK Ca channels exert a negative effect on uterine relaxation in late pregnancy. Leptin may have a physiological role in maintaining uterine quiescence in mid-pregnancy and its reduced relaxant response in late gestation may facilitate labor. Further, ObRb receptor agonists may be useful in the management of preterm labor.
Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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