Bradykinin causes contraction in rat uterus through the same signal pathway as oxytocin

Abstract

The signal pathway for bradykinin-induced contraction of the uterine smooth muscle was investigated by comparing the effect of blocking agents on bradykinin and oxytocin induced contractions of the isolated rat uterus in organ bath. The phospholipase C inhibitor U-73,122 abolished the effect of both bradykinin and oxytocin. Inhibition of non-voltage-dependent Ca2+ influx by SK & F 96,365 reduced the contraction induced by both agonists to about 20% of control. The tissues failed to contract when they were exposed to bradykinin or oxytocin in Ca(2+)-free Krebs-Henseleit buffer with 2 mM EDTA. Both bradykinin and oxytocin induced further contraction when the tissues were partially depolarized and partially contracted by 30 mM KCl. These observations suggest that bradykinin, like oxytocin, activates phospholipase C which generates IP3 with a subsequent release of Ca2+ from intracellular stores followed by store-operated Ca2+ influx. Thus, membrane potential independent steps appear to be important in bradykinin-induced contraction in the rat uterus.

Voltage‐dependent inhibition of the muscarinic cationic current in guinea‐pig ileal cells by SK&F 96365

“…In the present study we characterized the inhibitory action of the imidazole compound SK&F 96365, generally considered as a selective inhibitor of receptor‐mediated Ca 2+ entry, in particular of store‐operated Ca 2+ influx, which is the dominant Ca 2+ entry mechanism in nonexcitable cells (for a review see Parekh & Penner, 1997). In previous studies this drug was found to inhibit receptor‐stimulated Ca 2+ entry following store depletion in various cell types such as human platelets, neutrophils and endothelial cells (Merritt et al ., 1990), lymphocytes (Mason et al ., 1993), HL‐60 cells (Koch et al ., 1994), Jurkat T cells (Sei et al ., 1995) and in several different smooth muscles (Li et al ., 1997; Wayman et al ., 1997; Takemoto et al ., 1998; Wassdal et al ., 1998; Yang, 1998; Lagaud et al ., 1999). However, SK&F 96365 is neither very potent (the IC 50 in most cases around 10 μ M ) nor selective as it can also inhibit voltage‐gated Ca 2+ channels (Merritt et al ., 1990), K + channels (Schwarz et al ., 1994), the SR Ca 2+ ATPase (Mason et al ., 1993), stimulate phosphoinositide hydrolysis and cause intracellular Ca 2+ release (Arias‐Montano et al ., 1998) and facilitate nicotinic receptor desensitization (Hong & Chang, 1994).…”

Human effector/initiator gene sets that regulate myometrial contractility during term and preterm labor

“…Contractile responses of nonpregnant human myometrium to bradykinin are reduced during the luteal phase49. Wassdal et al noted that bradykinin contracted rodent myometrium via the same pathway as did oxytocin 50. In cultured decidua-derived cells, bradykinin stimulates the release of arachidonic acid, interleukin 6 (IL-6), and interleukin 8 (IL-8).…”

Estrogen-like effect of a Cimicifuga racemosa extract sub-fraction as assessed by in vivo, ex vivo and in vitro assays

“…In human myometrium and uterine arteries, ovarian steroids seem to cause a more pronounced inhibition of receptor-mediated than of voltage-dependent Ca 2+ channels [38]. On the other side, oxytocin, bradykinin and prostaglandin F 2␣ act by increasing intracellular Ca 2+ concentrations [32,39].…”