Receptor subtypes,multiplicity

Serotonin (5HT) Excitatory or inhibitory, depending on receptor subtype (multiple) with second messenger coupling (except 5HT3 subtype coupled directly to ion channel) activities modified by CNS stimulants, antidepressants, some anxiolytics. 

Waxman EA, Lynch DR (2005) N-methyl-D-aspartate receptor subtypes multiple roles in excitotoxicity and neurological disease. Neuroscientist 11 37-49... 

The opioid peptides vary in their binding affinities for the multiple opioid receptor types. Leu- and Met-enkephalin have a higher affinity for 5-receptors than for the other opioid receptor types (68), whereas the dynorphin peptides have a higher affinity for K-sites (69). P-Endorphin binds with equal affinity to both p- and 5-receptors, but binds with lower affinity to K-sites (70). The existence of a P-endorphin-selective receptor, the S-receptor, has been postulated whether this site is actually a separate P-endorphin-selective receptor or is a subtype of a classical opioid receptor is a matter of controversy (71,72). The existence of opioid receptor subtypes in general is quite controversial although there is some evidence for subtypes of p- (73), 5-(74), and K-receptors (72,75), confirmation of which may be obtained by future molecular cloning studies. 

Traditionally receptors have been classified according to their pharmacology. Each neurotransmitter acts on its own family of receptors and these receptors show a high degree of specificity for their transmitter. Thus, the receptors on which acetylcholine (ACh) works do not respond to glutamate (or any other neurotransmitter) and vice versa. Diversity of neurotransmitter action is provided by the presence of multiple receptor subtypes for each neurotransmitter, all of which still remain specific to that neurotransmitter. This principle is illustrated by the simple observations outlined in... 

The acute CNS effects of MDMA administration are mediated by the release of monoamine transmitters, with the subsequent activation of presynaptic and postsynaptic receptor sites.40 As specific examples in rats, MDMA suppresses 5-HT cell firing, evokes neuroendocrine secretion, and stimulates locomotor activity. MDMA-induced suppression of 5-HT cell firing in the dorsal and median raphe involves activation of presynaptic 5-HT1A autoreceptors by endogenous 5-HT.4142 Neuroendocrine effects of MDMA include secretion of prolactin from the anterior pituitary and corticosterone from the adrenal glands 43 Evidence supports the notion that these MDMA-induced hormonal effects are mediated via postsynaptic 5-HT2 receptors in the hypothalamus, which are activated by released 5-HT. MDMA elicits a unique profile of locomotor effects characterized by forward locomotion and elements of the 5-HT behavioral syndrome such as flattened body posture, Straub tail, and forepaw treading.44 6 The complex motor effects of MDMA are dependent on monoamine release followed by activation of multiple postsynaptic 5-HT and DA receptor subtypes in the brain,47 but the precise role of specific receptor subtypes is still under investigation. 

Dopamine receptors are found primarily in brain, although they also exist in kidney [33]. Two subtypes of dopamine receptor were initially identified based primarily on differences in their drug specificities and signaling mechanisms. D receptors were found to stimulate adenylyl cyclase activity, while D2 receptors inhibited this enzyme (Fig. 12-6). Subsequently, multiple Dr and D2-like receptors were identified by molecular cloning (Table 12-3) [33], All dopamine receptor subtypes are... 

Hirbec, H., Perestenko, O., Nishimune, A., Meyer, G., Nakanishi, S., Henley, J. M., and Dev, K. K. (2002) The PDZ proteins PICK1, GRIP, and syntenin bind multiple glutamate receptor subtypes. Analysis of PDZ binding motifs. J. Biol. Chem. 277,15221-15224. 

As is discussed in greater detail later, it has been impossible to identify pharmacologically distinct subunits. This despite the fact that pharmacological differences were observed in vivo, which suggested the existence of multiple receptor subtypes. Specifi-... 

Millan Ml, Maiofiss L, Cussac D, Audinot V, Boutin JA, Newman-Tancredi A. (2002) Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drags at 21 native and cloned human receptor subtypes. J Pharmacol Exp Ther 303 791-804. 

Many other neurotransmitters are undoubtedly involved in reward systems (Nutt, 1996). These include cholecystokinin, glutamate, neuropeptide Y, anan-damides and others, each of which have many other actions and also act on multiple receptor subtypes. These substances not only interact with other reward neurotransmitters but also take part in a delicate balance of activity with reciprocally connected punishment systems. 

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