Endogenous morphine: opening new doors for the treatment of pain and addiction.
Nitric oxide (NO) signalling is at the forefront of intense research interest because its many effects remain controversial and seemingly contradictory. This paper examines its role as a potential mediator of pain and tolerance. Within this context discussion covers endogenous morphine, documenting its ability to be made in animal tissues, including nervous tissue, and in diverse animal phyla. Supporting morphine as an endogenous signalling molecule is the presence of the newly cloned mu3 opiate receptor subtype found in animal (including human) immune, vascular and neural tissues, which is coupled to NO release. Importantly, this mu opiate receptor subtype is morphine-selective and opioid peptide-insensitive, further highlighting the presence of morphinergic signalling coupled to NO release. These findings provide novel insights into pain and tolerance as morphinergic signalling exhibits many similarities with NO actions. Taken together, a select morphinergic signalling system utilising NO opens the gate for the development of novel pharmaceuticals and/or the use of old pharmaceuticals in new ways.
Pryor
Stephen C
SC
State University of New York--College at Old Westbury, Neuroscience Research Institute, Old Westbury, NY 11568, USA.
Zhu
Wei
W
Cadet
Patrick
P
Bianchi
Enrica
E
Guarna
Massimo
M
Stefano
George B
GB
D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D000701:Analgesics, Opioid / Q000627:therapeutic use; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism; D004361:Drug Tolerance; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007276:Injections, Intraventricular; D008969:Molecular Sequence Data; D009020:Morphine / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use; D009021:Morphine Dependence / Q000378:metabolism* / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010146:Pain / Q000188:drug therapy / Q000378:metabolism* / Q000523:psychology; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D000700:Analgesics; D000701:Analgesics, Opioid; D004791:Enzyme Inhibitors; D017450:Receptors, Opioid, mu; D009569:Nitric Oxide; D009020:Morphine; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP