Peptide receptor systems

Recently, nonpeptide compounds have been developed for many peptide receptor systems. These compounds, which usually are discovered through screening of chemical files, generally do not resemble the corresponding peptide ligands chemically. Nevertheless, they act as specific and... 

Control of feeding behavior involves peripheral peptides (insulin, ghrelin, leptin) plus several peptides in the CNS (orexins/hypocretins, CCK, galanin, MSH, neuropeptide Y, CRH, cocaine-and-amphetamine-regulated transcript (CART)) [35, 36]. Some of the same peptides are involved in reward systems crucial to drug addiction. Specific receptor blockers are being tested for many of these peptide-receptor systems, with the hope of very selective actins with minimal side effects [35], For example, there are two CCK receptor subtypes, CCK-A and... 

There are now many examples of novel peptide transmitter systems that have been identified through orphan receptor ligand screening and greatly impacted the basic understanding of human physiology. Prime examples for the discovery of novel transmitter with therapeutic implications are the neuropeptides orphaninFQ/... 

Carrero I, Femandez-Moreno MD, Perez-Albarsanz MA, et al. 1989. Lindane effect upon the vasoactive intestinal peptide receptor-effector system in rat enterocytes. Biochem Biophys Res Comm 159(3) 1391-1396. 

Fig. 11.1. Principle of an immunological synapse. Possibilities for communication between B and T cells during an immune response. Antigenic peptides are presented by the MHC complex class II at the surface of the B cell. The antigens are recognized and bound by T cell receptors of the T cell. The T cell receptor is activated and sets a signal chain in motion that leads to activation of the expression of cytokines, such as IL-2. The cytokine is secreted, and binds and activates a cytokine receptor on the B cell. TNFa is shown as another example of a ligand-receptor system. TNFa communicates, as a membrane-bound ligand, with a corresponding receptor on the surface of the B cell. The interactions shown take place in a narrow spatial region between B and T cells, which is why this system is referred to as an immunological synapse. TNF tumor necrosis factor MHC major histocompatibility complex IL-2 interleukin 2.

Sklar, L. A., Sayre, J., McNeil, V. M., and Finney, D. A. (1985). Competitive binding kinetics in ligand-receptor-competitor systems. Rate parameters for unlabeled ligands for the formyl peptide receptor. Mol. Pharmacol. 28, 323-330. 

Many cells, such as lymphocytes, do however lack efficient internalizing receptor systems. The development of a new and effective internalizing pathway thus appears as a very important goal. Weissleder et al. [83, 96] have tried to develop such a system by attaching a superparamagnetic iron oxide to a membrane translocating signal (MTS) peptide. Several MTSs have been described... 

Smith BN, Davis SF, van den Pol AN et al (2002) Selective enhancement of excitatory synaptic activity in the rat nucleus tractus solitarius by hypocretin 2. Neuroscience 115 707-14 Smith-White MA, Herzog H, Potter EK (2002) Role of neuropeptide Y Y2 receptors in modulation of cardiac parasympathetic neurotransmission. Regul Peptides 103 105-11 Stanford IM, Cooper Al (1999) Presynaptic mu and delta opioid receptor modulation of GABAa IPSCs in the rat globus pallidus in vitro. 1 Neurosci 19 4796 4803 Starke K (1977) Regulation of noradrenaline release by presynaptic receptor systems. Rev Physiol Biochem Pharmacol 77 1-124... 

While the above studies show that gross accumulation or patching and endocytosis of the GnRH-receptor complex is not a prerequisite for GnRH action, they do not exclude the possibility that dimerization or microaggregation of the receptors are required to stimulate LH release. For other peptide hormone systems, such as in-... 

Seifert, R., and Wenzel-Seifert, K. (2003). The human formyl peptide receptor as model system for constitutively active G-protein-coupled receptors. Life Sci. 73, 2263-2280. 

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