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, cardiovascul ar and nervous systems. The synthesizing enzyme, nitric oxide synthase (NOS ) occurs in three forms: endothelial (e), neuronal (n) and inducible (i) NO S. The first two are constitutively expressed. We surmise that in many tiss ues 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 a ctions of NO really deal with iNOS-derived NO. We make the case that cNOS i s responsible for a basal or 'tonal' level of NO; that this NO keeps partic ular types of cells in a state of inhibition and that activation of these c ells occurs through disinhibition. Furthermore, naturally occurring signali ng molecules such as morphine, anandamide, interleukin-10 and 17-beta-estra diol appear to exert, in part, their beneficial physiological actions, i.e. , immune and endothelial down regulation by the stimulation of cNOS. In reg ard to opiates, we demonstrate the presence of a human endothelial mu opiat e receptor by RT-PCR and sequence determination: further substantiating the role of opiates in vascular couplings 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. (C) 2000 Elsevier Sc ience Ltd. All rights reserved.