Table 2.

Inhibition of uterine contractility

Factor	Mechanism
Endogenous
Reduced oxytocin receptors	Decreased uterine response to oxytocin (maternal/endogenous or pharmacologic/exogenous) during labor[57]
Reduced gap junctions	Decreased propagation of uterine depolarization leading to disrupted or inefficient contraction coordination[28, 136]
Reduced COX-2	Inhibited labor signaling via decreased prostaglandin production[137]
Acidification	Nonspecific blockade of calcium ion influx, disrupted calcium/MLCK coupling, and dysregulated uterine contraction coordination[23, 57]
Exogenous
Calcium channel blocker (e.g., nifedipine)	Decreased intracellular calcium levels[138]
Oxytocin receptor antagonist (e.g., atosiban)	Inhibited oxytocin and vasopressin receptor stimulation of ER calcium release[138]
Beta-adrenergic receptor agonist (e.g., terbutaline)	Increased adenylyl cyclase production of cAMP to activate PKA which decreases MLCK activity[138]
COX-2 inhibitor (e.g., indomethacin)	Blocked labor-stimulating prostaglandin production[137, 138]

COX-2 cyclooxygenase 2, MLCK myosin light chain kinase, PKA protein kinase A, cAMP cyclic adenosine monophosphate, ER endoplasmic reticulum