Emergent Concepts of Receptor Pharmacology

2019 ◽  
pp. 17-41 ◽  
Author(s):  
Terry Kenakin
Keyword(s):  
Receptor Pharmacology

Cholecystokinin receptors

1995 ◽  
Vol 269 (5) ◽  
pp. G628-G646 ◽  
Author(s):  
S. A. Wank
Keyword(s):  
Function Analysis ◽  
Receptor Gene ◽  
Wide Distribution ◽  
Receptor Expression ◽  
Receptor Subtypes ◽  
Cck Receptors ◽  
High Affinity ◽  
Recombinant Receptor ◽  
Receptor Pharmacology ◽  
Specific Variation

The cholecystokinin (CCK) and gastrin families of peptides act as hormones and neuropeptides on central and peripheral CCK receptors to mediate secretion and motility in the gastrointestinal (GI) tract in the physiological response to a normal meal. CCK and its receptors are also widely distributed in the central nervous system (CNS) and contribute to the regulation of satiety, anxiety, analgesia, and dopamine-mediated behavior. Although the wide distribution, myriad number of functions, and reported pharmacological heterogeneity of CCK receptors would suggest a large number of receptor subtypes, the application of modern molecular biological techniques has identified two CCK receptors, CCK-A receptor (CCK-AR) and CCK-B receptor (CCK-BR), that mediate the actions of CCK and gastrin; gastrin receptors have been found to be identical to CCK-BR. CCK-AR, found predominantly in the GI system and select areas of the CNS, have high affinity for CCK and the nonpeptide antagonist L-364,718, whereas CCK-BR, found predominantly in the CNS and select areas of the GI system, have high affinity for CCK and gastrin and the nonpeptide antagonist L-365,260. Both CCK-AR and CCK-BR are highly conserved between species, although there is some tissue-specific variation in expression. Recombinant receptor expression faithfully reproduces the native receptor pharmacology and signal transduction pathways, allowing direct comparisons of receptor function between species as well as serving as a convenient source of receptor. Our present knowledge of the chromosomal localization, receptor gene structure, and primary sequence will allow further studies in disease association, receptor regulation, and structure-function analysis.

GABAA receptor pharmacology

1996 ◽  
Vol 69 (3) ◽  
pp. 173-198 ◽  
Author(s):  
G.A.R. Johnston
Keyword(s):  
Gabaa Receptor ◽  
Receptor Pharmacology

Peptidases and smooth muscle cell angiotensin II receptor pharmacology

Peptides ◽  
1993 ◽  
Vol 14 (2) ◽  
pp. 345-352 ◽  
Author(s):  
Robert B. Cohen ◽  
Maria L. Webb ◽  
Kenneth E.J. Dickinson
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Angiotensin Ii Receptor ◽  
Receptor Pharmacology

scholarly journals Type 1 angiotensin receptor pharmacology: Signaling beyond G proteins

2007 ◽  
Vol 113 (1) ◽  
pp. 210-226 ◽  
Author(s):  
Cristina Oro ◽  
Hongwei Qian ◽  
Walter G. Thomas
Keyword(s):  
G Proteins ◽  
Angiotensin Receptor ◽  
Receptor Pharmacology

scholarly journals Are GPCRs Still a Source of New Targets?

2013 ◽  
Vol 18 (9) ◽  
pp. 947-966 ◽  
Author(s):  
Stephen L. Garland
Keyword(s):  
Drug Targets ◽  
Protein Complexes ◽  
X Ray Crystallography ◽  
Peptide Family ◽  
Wide Range ◽  
The Family ◽  
Receptor Pharmacology ◽  
Technical Advances ◽  
Allosteric Mechanisms ◽  
G Protein Coupled

G-protein–coupled receptors (GPCRs) still offer enormous scope for new therapeutic targets. Currently marketed agents are dominated by those with activity at aminergic receptors and yet they account for only ~10% of the family. Progress up until now with other subfamilies, notably orphans, Family A/peptide, Family A/lipid, Family B, Family C, and Family F, has been, at best, patchy. This may be attributable to the heterogeneous nature of GPCRs, their endogenous ligands, and consequently their binding sites. Our appreciation of receptor similarity has arguably been too simplistic, and screening collections have not necessarily been well suited to identifying leads in new areas. Despite the relative shortage of high-quality tool molecules in a number of cases, there is an emerging, and increasingly substantial, body of evidence associating many as yet “undrugged” receptors with a very wide range of diseases. Significant advances in our understanding of receptor pharmacology and technical advances in screening, protein X-ray crystallography, and ligand design methods are paving the way for new successes in the area. Exploitation of allosteric mechanisms; alternative signaling pathways such as G12/13, Gβγ, and β-arrestin; the discovery of “biased” ligands; and the emergence of GPCR-protein complexes as potential drug targets offer scope for new and much improved drugs.

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