Neuropeptide receptor-acting

Expressions of peptide receptors and the corresponding peptides are not well matched. Neuropeptides can act at... 

Endorphins, dynorphins, and enkephalins are a particularly interesting group of neuropeptides. They act as endogenous opiates by producing analgetic, sedative, and euphoriant effects in extreme situations. Drugs such as morphine and heroin activate the receptors for these peptides (see p. 354). 

Figure 4 shows how a presynaptic neuropeptide Y receptor was identified in a superfusion model. In mouse brain cortex slices, serotonin release was concentration-dependently inhibited by neuropeptide Y and this effect was potently mimicked by neuropeptide Y-(13-36). Since the latter is selective for Y2 over Yi andYs receptors (Alexander et al. 2006) one may conclude that neuropeptide Y acts via Y2 receptors. 

Fig. 4 Effect of various peptides and nonpeptides on the electrically (3 Hz) evoked tritium overflow from superfused mouse brain cortex slices preincubated with 3H-serotonin. The evoked overflow represents quasi-physiological exocytotic serotonin release. In all experiments, serotonin autoreceptors were blocked by metitepine. The figure shows that human neuropeptide Y concentration-dependently inhibited serotonin release and that this effect was mimicked by human neuropeptide Y (13-36) (NPYi3 36), which has a high affinity for Y2 but a very low affinity for Yi receptors. These results are compatible with the view that neuropeptide Y acts via Y2 receptors in the present model. For the sake of comparison, the figure also shows the inhibitory effects of another three agonists, acting via cannabinoid CBi, histamine H3 and prostaglandin EP3 receptors and used at concentrations causing the maximum or near-maximum effect at their respective receptors. Drug concentrations in pM. P < 0.05, P < 0.003, compared to the control (from Nakazi et al. 2000 and Nakazi 2001 redrawn).

Grundemar, L., Wahlestedt, C. Reis, DJ. (1991b) Neuropeptide Y acts at an atypical receptor to evoke cardiovascular depression and to inhibit glutamate responsiveness in the brainstem. J. Pharmacol. Exp. Ther. 258, 633-638. 

Cotransmission is transmission through a single synapse by means of more than one transmitter. For example, to elicit vasoconstriction, postganglionic sympathetic neurones release their classical transmitter noradrenaline (which acts on smooth muscle a-adrenoceptors) as well as ATP (which acts on smooth muscle P2 receptors) and neuropeptide Y (which acts on smooth muscle Yx receptors). 

The hormone pancreatic polypeptide (PP) is a 36 amino acid peptide, which is closely related to neuropeptide Y and peptide YY PP is mainly found in pancreatic cells distinct from those storing insulin, glucagon or somatostatin. It acts on receptors that belong to the family of neuropeptide Y receptors, particularly on the Y4 subtype. 

Purinergic System. Figure 2 Schematic of sympathetic cotransmission. ATP and NA released from small granular vesicles (SGV) act on P2X and a-i receptors on smooth muscle, respectively. ATP acting on inotropic P2X receptors evokes excitatory junction potentials (EJPs), increase in intracellular calcium ([Ca2+]j) and fast contraction while occupation of metabotropic ar-adrenoceptors leads to production of inositol triphosphate (IP3), increase in [Ca2+]j and slow contraction. Neuropeptide Y (NPY) stored in large granular vesicles (LGV) acts after release both as a prejunctional inhibitory modulator of release of ATP and NA and as a postjunctional modulatory potentiator of the actions of ATP and NA. Soluble nucleotidases are released from nerve varicosities, and are also present as ectonucleotidases. (Reproduced from Burnstock G (2007) Neurotransmission, neuromodulation cotransmission. In Squire LR (ed) New encyclopaedia of neuroscience. Elsevier, The Netherlands (In Press), with permission from Elsevier). 

Figure 17.1. Neurotransmission (specific case of peptidergic cells). Production of the peptides in the cel I body (1). Packing of the peptides i nto large dense core vesicles for further transport to the axons (2). Release of neuropeptides from the cell soma (3) dendrites (4) and outside of the synapse (5). Release of classic neurotransmitters in the synaptic cleft (6). G-protein-coupled type receptors, which act as peptide receptors. (See color insert.)...

Figure 4.1. Model of neurogenic inflammation. Stimulation at the skin initiates orthodromic impulses in sensory nerve receptors which elicit antidromic impulses in branching collaterals. The release of neuropeptides such as calcitonin gene-related peptide (CGRP), substance P (SP), and somatostatin (SOM) from nerve terminals ensues and they in turn stimulate the release of histamine (H) and the generation of leukotrienes (LT) from nearby mast cells. These mediators then produce vasodilatation and an increase in vascular permeability. In addition, they act on the nerve terminal to produce further...

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