Basal nitric oxide limits immune, nervous and cardiovascular excitation: human endothelia express a mu opiate receptor.
Nitric oxide (NO) is a major signaling molecule in the immune, cardiovascular and nervous systems. The synthesizing enzyme, nitric oxide synthase (NOS) occurs in three forms: endothelial (e), neuronal (n) and inducible (i) NOS. The first two are constitutively expressed. We surmise that in many tissues there is a basal level of NO and that the actions of several signaling molecules initiate increases in cNOS-derived NO to enhance momentary basal levels that exerts inhibitory cellular actions, via cellular conformational changes. It is our contention that much of the literature concerning the actions of NO really deal with i-NOS-derived NO. We make the case that cNOS is responsible for a basal or 'tonal' level of NO; that this NO keeps particular types of cells in a state of inhibition and that activation of these cells occurs through disinhibition. Furthermore, naturally occurring signaling molecules such as morphine, anandamide, interleukin-10 and 17-beta-estradiol appear to exert, in part, their beneficial physiological actions, i.e., immune and endothelial down regulation by the stimulation of cNOS. In regard to opiates, we demonstrate the presence of a human endothelial mu opiate receptor by RT-PCR and sequence determination, further substantiating the role of opiates in vascular coupling to NO release. Taken together, cNOS derived NO enhances basal NO actions, i.e., cellular activation state, and these actions are further enhanced by iNOS derived NO.
Stefano
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GB
Neuroscience Research Institute, State University of New York at Old Westbury, 11568-0210, USA. stefanog@surg.som.sunysb.edu
Goumon
Y
Y
Bilfinger
T V
TV
Welters
I D
ID
Cadet
P
P
D000818:Animals; D001483:Base Sequence / Q000235:genetics; D002320:Cardiovascular Physiological Phenomena; D004727:Endothelium / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000502:physiology*; D008969:Molecular Sequence Data; D009424:Nervous System Physiological Phenomena; D009569:Nitric Oxide / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000378:metabolism
D017450:Receptors, Opioid, mu; D009569:Nitric Oxide