Interactions between morphine and nitric oxide in various organs.

Nitric oxide (NO) plays obligatory roles as an important intercellular messenger in the control of physiological functions and it also participates in pathophysiological interventions. This labile, gaseous molecule is also involved in mechanisms underlying the beneficial and untoward actions of therapeutic agents. Endogenous NO is formed by endothelial and neurogenic NO synthases that are constitutively present mainly in the endothelium and nervous system, respectively, and is induced by lipopolysaccharides or cytokines mainly in mitochondria, glial cells, and vascular smooth muscle cells. NO modulates the effects of morphine on processes involving the central nervous system, such as learning, memory, convulsion, thermoregulation, and penile erection. This molecule is also involved in the modification of morphine actions on the cardiovascular, digestive, and respiratory systems. Morphine regulates NO bioavailability in various organs. NO formed by inducible NO synthase participates in some morphine actions in the immune system. Information concerning interactions between NO and morphine and other opioids in a variety of organs and tissues is quite useful in establishing new strategies for minimizing the noxious and unintended reactions that are frequently encountered during analgesic therapy.