Mechanism of Oxytocin-Induced Contraction in Rat Gastric Circular Smooth Muscle

Abstract

Oxytocin produces an excitatory effect on gastric muscle through the activation of receptors present on stomach smooth muscle cells. However, the intracellular mechanisms that mediate oxytocin excitatory effects are still largely unknown. Therefore, we aimed to investigate the signaling pathways involved in oxytocin-induced contractions in gastric smooth muscle, shedding light on phospholipase C (PLC)-β1 signaling and its downstream molecules, including inositol 1,4,5- trisphosphate (IP3) and myosin light chain kinase (MLCK). The contractions of gastric smooth muscle from male rats were measured in an organ bath set up in response to exogenous oxytocin 10−7 M, in the presence and absence of inhibitors of the indicated signaling molecules. Oxytocin (10−9–10−5 M) induced dose-dependent stomach smooth muscle contraction. Pre-incubation with atosiban, an oxytocin receptor inhibitor, abolished the oxytocin-induced contraction. Moreover, PLC β1 inhibitor (U73122) and IP3 inhibitor Xestospongin C inhibited oxytocin-induced muscle contraction to various degrees. Verapamil, a calcium channel blocker, inhibited oxytocin-induced contraction, and pre-incubation of the strips, with both verapamil and Xestospongin C, further inhibited the excitatory effect of oxytocin. Chelation of intracellular calcium with BAPT-AM (1,2-bis-(o-aminophenoxy) ethane-N,N,N′,N′-tetraacetic acid) significantly inhibited the effect of oxytocin on muscle contraction. Finally, pre-incubation of the strips with the Ca2+/calmodulin-dependent protein kinase selective inhibitor STO-609 significantly inhibited the contraction induced by oxytocin. These results suggest that oxytocin directly stimulates its cell surface receptor to activate PLC β1, which in turn liberates IP3, which eventually elevates intracellular calcium, the prerequisite for smooth muscle contraction.

Electroacupuncture Ameliorates Gastrointestinal Motility in Rats with Functional Dyspepsia Via PLC/IP3 Signaling

“…U73122 is an aminosteroid PLC inhibitor that prevents Ca 2+ release from the ER by reducing the availability of the PLC substrate PIP 2 26,49 . PLC inhibitor (U73122) and IP 3 inhibitor (Xestospongin C) can differentially inhibit the contraction of gastric smooth muscles induced by contractile hormones in rats 50 . Pretreatment with U73122 reduced the high intracellular Ca 2+ concentration induced by the PLC-IP 3 pathway 51 .…”

Oxytocin: An expansive review of its mechanisms, functions, and therapeutic potential

“…Oxytocin has been found to modulate cardiovascular parameters, including blood pressure and heart rate, suggesting a potential role in cardiovascular homeostasis [8]. It also influences gastrointestinal motility and gut functions, and emerging evidence points to its immunomodulatory properties [9,10]. Additionally, oxytocin has been implicated in pain modulation, with studies demonstrating its analgesic effects and potential in pain management [11].…”