Neuromodulators types

It is important to point out that some types of placebo analgesia appear to be insensitive to naloxone, thus suggesting that neuromodulators other than opioids can be involved in some circumstances. For example, if a placebo is given after repeated administrations (preconditioning) of the non-opioid painkiller ketorolac, the placebo analgesic response is not blocked by naloxone. 

Lauro C, Di Angelantonio S, Cipriarri R et al (2008) Activity of adenosine receptors type 1 is required for CX3CLl-mediated neuroprotection and neuromodulation in hippocampal neurons. J Immunol 180 7590-7596... 

Type III neurotransmitters These are peptides (neuropeptides), and most are considered to be neuromodulators rather than neurotransmitters. As a further complication, some of these are also found in the intestine, where they act as local hormones or even endocrine hormones (Chapter 4 Table 14.1). 

Only the first type of neurotransmitter release mediates the fast point-to-point synaptic transmission process at classical synapses (sometimes referred to as wiring transmission). All of the other types of neurotransmitter release effect one or another form of volume transmission whereby the neurotransmitter signal acts diffusely over more prolonged time periods (Agnati et al., 1995). Of these volume transmitter pathways, the time constants and volumes involved differ considerably. For example, diffusible neurotransmitters such as nitric oxide act relatively briefly in a localized manner, whereas at least some neuropeptides act on the whole brain, and can additionally act outside of it (i.e., function as hormones). There is an overlap between wiring and volume neurotransmission in that all classical neurotransmitters act as wiring transmitters via ionotropic receptors, and also act as volume transmitters via G-protein-coupled receptors. Moreover, neuromodulators in turn feed back onto classical synaptic transmission. 

NO is an important neuromodulator in the retina, and is implicated in many physiological processes (Goldstein et al., 1996). NO is synthesized from arginine via the action of nitric oxide synthase (NOS). Three distinct isoforms of NOS have been identified. Neuronal NOS (nNOS) and endothelial NOS (eNOS) are Ca -dependent. nNOS is constitutively expressed by certain types of amacrine cells in the retina. These cells often have long projections in the irmerplexiform layer (Sharma et al., 1997 Sharma et al., 2001). eNOS is expressed by the endothelial cells of blood vessels (Cheon et al., 2003). iNOS is Ca -independent and expressed in Muller and RPE cells in response to certain stimuli (Lopez-Costa et al., 1997). Activation of the NMDA receptor leads to an increase in intracellular calcium levels, which can induce expression of, and activate NOS isoforms, either directly (nNOS) or via the activation of calcium-dependent protein kinase C (PKC) (Lipton, 1999) (O Figure 3-6). 

Sugiura T, Kodaka T, Kondo S, Tonegawa T, Nakane S, Kishimoto S, Yamashita A, Waku K (1997b) Inhibition by 2-arachidonoylglycerol, a novel type of possible neuromodulator, of the depolarization-induced increase in intracellular free calcium in neuroblastoma x glioma hybrid NG108-15 cells. Biochem Biophys Res Commun 233 207-210... 

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