A-Receptor

M.p. 103°C. Noradrenaline is released in the adrenal medulla with adrenaline, and also at the sympathetic nerve endings. Its release from a nerve fibre is followed by binding to a receptor molecule on the next nerve or muscle fibre, probably causing a change in the electrical charge of the receptor-cell membrane. Biosynthetically it normally serves as a precursor for adrenaline. 

Agonist An agonist is a receptor ligand mediating a receptor response (intrinsic effect). 

Antagonist An antagonist is a receptor ligand preventing the action of an agonist, in a direct (competitive) or indirect (allosteric) manner. 

Example If a drug molecule interacts with a receptor molecule through hydrogen bonds, then yon might restrain the distance between the donor and acceptor atoms involved in the hydrogen bonds. During a molecular dynamics simulation, these atoms would slay near an ideal value, while the rest of the molecular system fully relaxes. 

Desjarlais R L, R P Sheridan, G L Seibel, J S Dixon, ID Kuntz and R Venkataraghavan 1988. Using Shap Complementarity as an Initial Screen in Designing Ligands for a Receptor Binding Site of Know Three-Dimensional Structure. Journal of Medicinal Chemistry 31 722-729. 

Information may be stored in the architecture of the receptor, in its binding sites, and in the ligand layer surrounding the bound substrate such as specified in Table 1. It is read out at the rate of formation and dissociation of the receptor—substrate complex (14). The success of this approach to molecular recognition ties in estabUshing a precise complementarity between the associating partners, ie, optimal information content of a receptor with respect to a given substrate. 

Fig. 1. Schematic representation of a receptor—substrate (host—guest) complex involving cavity inclusion of the substrate and the formation of different types of weak supramolecular interactions between receptor (hatched) and substrate (dotted).

Fig. 2. Principle mechanisms of formation of a receptor—substrate complex (a) Fischer s rigid "lock-and-key" model (b) "induced fit" model showing...

Selection of pollution control methods is generally based on the need to control ambient air quaUty in order to achieve compliance with standards for critetia pollutants, or, in the case of nonregulated contaminants, to protect human health and vegetation. There are three elements to a pollution problem a source, a receptor affected by the pollutants, and the transport of pollutants from source to receptor. Modification or elimination of any one of these elements can change the nature of a pollution problem. For instance, tall stacks which disperse effluent modify the transport of pollutants and can thus reduce nearby SO2 deposition from sulfur-containing fossil fuel combustion. Although better dispersion aloft can solve a local problem, if done from numerous sources it can unfortunately cause a regional one, such as the acid rain now evident in the northeastern United States and Canada (see Atmospheric models). References 3—15 discuss atmospheric dilution as a control measure. The better approach, however, is to control emissions at the source. 

Fig. 4. FSH receptor-binding potencies of equine FSH ( ), eCG purified from pregnant mate s semm (O), and endometrial cups (A). Receptor-binding in ceU membrane fractions, B/Bq from (a) horse, (b) calf, and (c) rodent testes (40). Courtesy of Butterworth-Heinemaim.

The principal organs involved in the peripheral clearance of hGH from the plasma are the kidney and fiver. hGH is cleared via glomerular filtration at the kidney and by a receptor-mediated mechanism at the fiver (58,59). In animal models, derivatives of hGH such as the 20,000 mol wt variant, oligomeric forms, and hGH complexed with GH-binding protein have been shown to be cleared from the semm at significandy lower rates than 22,000 mol wt hGH (60—62). The prolonged plasma half-life of these derivatives probably reflects a combination of decreased receptor affinity and size constraints on glomerular filtration. 

The BZ stmcture also has provided a molecular scaffold for a number of peptide receptor ligands (26). Antagonists for the cholecystokinin (CCK-A) receptor, eg, devazepide (65), the thyrotropin-releasing hormone (TRH) receptor, eg, midazolam (66), and the /i -opiate receptor, eg, tifluadom (67), as well as a series of ras famyl transferase inhibitors, eg, BZA-2B (68) (30) have been identified (Table 4). 

Phentolamine (87), WB 4101 (88), and the site directed alkylatiag agent, chloroethylclonidine (CEC) (89) have been traditionally used to define a -receptors. Table 6 Hsts the various catecholamines and adrenoreceptor agonists and antagonists. 

Phenylephrine (90) is a selective receptor agonist (+)-niguldipine (91) is a selective antagonist for the receptor. Pra2osin (92) and 5-methylurapidil (93) are nonselective a -receptor antagonists. CEC can differentiate receptors from the other receptors. Pra2osin has low and high affinity for and receptors, respectively. 

The class III cytokine receptor family includes two TNE receptors, the low affinity NGE receptor and 7-ceU surface recognition sites that appear to play a role in proliferation, apoptosis, and immunodeficiency. TNE-a (- 17, 000 protein) is produced by astrocytes and microglia and can induce fever, induce slow-wave sleep, reduce feeding, stimulate prostaglandin synthesis, stimulate corticotrophin-releasing factor and prolactin secretion, and reduce thyroid hormone secretion. TNE-a stimulates IL-1 release, is cytotoxic to oligodendrocytes, and reduces myelination this has been impHcated in multiple sclerosis and encephalomyelitis. Astrocyte TNE-a receptors mediate effects on IL-6 expression and augment astrocytic expression of MHC in response to other stimulants such as lEN-y. 

NMD A receptors are selectively activated by A/-methyl-D-aspartate (NMD A) (182). NMD A receptor activation also requires glycine or other co-agonist occupation of an allosteric site. NMDAR-1, -2A, -2B, -2C, and -2D are the five NMD A receptor subunits known. Two forms of NMDAR-1 are generated by alternative splicing. NMDAR-1 proteins form homomeric ionotropic receptors in expression systems and may do so m situ in the CNS. Functional responses, however, are markedly augmented by co-expression of a NMDAR-2 and NMDAR-1 subunits. The kinetic and pharmacological properties of the NMD A receptor are influenced by the particular subunit composition. 

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