Bombesin and bradykinin increase inositol phosphates and cytosolic free Ca2+, and stimulate DNA synthesis in human endometrial stromal cells

Abstract

The present studies were carried out to investigate the effect of several growth factors on human endometrial stromal cells. In human endometrial stromal cells, bombesin and bradykinin provoked an increase in intracellular free Ca2+ and in labelled inositol phosphates when pre-incubated with [3H]myoinositol. Some or possibly all of the initial increase in intracellular free Ca2+ represented a mobilization of Ca2+ from intracellular stores and the second phase of the response depended on Ca2+ influx from the extracellular medium. [3H]Thymidine was added to human cultured endometrial stromal cells with bombesin, bradykinin, epidermal growth factor (EGF), prostaglandin F2 alpha, vasopressin and platelet-derived growth factor. Bombesin, bradykinin and EGF stimulated the incorporation of [3H]thymidine into DNA in quiescent cells. In conclusion, bombesin and bradykinin are growth factors which activate phospholipase C in human endometrial stromal cells, while EGF stimulates DNA synthesis without the activation of phospholipase C.

International Union of Pharmacology. LXVIII. Mammalian Bombesin Receptors: Nomenclature, Distribution, Pharmacology, Signaling, and Functions in Normal and Disease States

“…BB 2 receptor activation stimulates growth of normal endometrial stomal cells (Endo et al, 1991), bronchial epithelial cells (Willey et al, 1984;Siegfried et al, 1993), melanocytes (Terashi et al, 1998), chondrocytes (Hill and McDonald, 1992), and normal enterocyte growth and turnover after small bowel resection (Chu et al, 1995;Sukhotnik et al, 2007) as well as normal development of the intestinal villus (Carroll et al, 2002) and normal fetal lung development (Emanuel et al, 1999;Shan et al, 2004). The effects of BB 2 receptor activation on neoplastic growth have been extensively studied (Moody et al, 1992;Jensen et al, 2001;Patel et al, 2006).…”

Tyrosine 220 in the 5th Transmembrane Domain of the Neuromedin B Receptor Is Critical for the High Selectivity of the Peptoid Antagonist PD168368

“…These peptides have important effects in the central nervous system including thermoregulation (21), satiety (22), control of circadian rhythm (23), and in peripheral tissues causing stimulation of gastrointestinal hormone release (18,24,25), activation of macrophages (26), and effects on development (27,28). These peptides also have potent growth effects causing proliferation of normal cells (18,29) and various tumor cell lines (18,30). The NMBR and GRPR are members of the bombesin receptor family within the GPCR superfamily and share ϳ50% overall amino acid sequence identity (19,20).…”

Localization and Expression of Gastrin-releasing Peptide (GRP) in the Bovine Cervix

“…Thus, expression of estrogen receptor (ER) in uterine cells later in development, as described for cows [39], may define the point at which estrogen begins to elicit trophic effects on the fetal uterus and/or increase the sensitivity of ER uterine target cells to paracrine mediators of estrogen action such as isulin-like growth factor I or epidermal growth factor. Since GRP has also been known as growth factor in endometrial tissue [12,13], it may take part in further prenatal development of the uterus because of its proliferation and differentiation capacities, and/or acting as a paracrine mediator of estrogen action.…”

“…In the female reproductive tract, GRP exhibits various physiological effects, such as control of epithelial ion transport in the endometrium [12] and modulation of uterine contraction [11] and also has effects on the proliferation and differentiation of the endometrium [13]. Furthermore, it serves as a cir cul at ing h or m on e i n fetal and uter ine development [14], as a mitogenic agent [15], and as an autocrine and paracrine regulatory peptide [16] i n th e u t e r u s .…”