Morphine enhances nitric oxide release in the mammalian gastrointestinal tract via the μ3 opiate receptor subtype: A hormonal role for endogenous morphine

Studies from our laboratory have revealed a novel μ opiate receptor, μ₃, which is expressed in both human vascular tissues and leukocytes. The μ₃, receptor is selective for opiate alkaloids, insensitive to opioid peptides and is coupled to constitutive nitric oxide (cNO) release. We now identify the μ₃ receptor characteristics in mammalian gut tissues. It appears that the various regions of the mouse gut release low levels of NO (0.02 to 4.6 nM) in a pulsatile manner. We demonstrate that morphine stimulates cNO release (peak level 17 nM) in the mouse stomach, small intestine and large intestine in a naloxone and L-NAME antagonizable manner. Opioid peptides do not exhibit cNO-stimulating capabilities in these tissues. Taken together, we surmise morphine acts as a hormone to limit gut activity via μ₃ coupled to NO release since μ opiate receptors are found in the gut and endogenous morphine is not but is found in blood.