Lactams as EP4 Prostanoid Receptor Subtype Selective Agonists. Part 1. 2-Pyrrolidinones — Stereochemical and Lower Side-Chain Optimization.

ChemInform ◽  
2004 ◽  
Vol 35 (34) ◽  
Author(s):  
Todd R. Elworthy ◽  
et al. et al.
Keyword(s):  
Side Chain ◽  
Receptor Subtype ◽  
Lower Side ◽  
Prostanoid Receptor ◽  
Selective Agonists ◽  
Subtype Selective

Lactams as EP4 prostanoid receptor subtype selective agonists. Part 1: 2-Pyrrolidinones-stereochemical and lower side-chain optimization

2004 ◽  
Vol 14 (7) ◽  
pp. 1655-1659 ◽  
Author(s):  
Todd R. Elworthy ◽  
Denis J. Kertesz ◽  
Woongki Kim ◽  
Michael G. Roepel ◽  
Lina Quattrocchio-Setti ◽  
...  
Keyword(s):  
Side Chain ◽  
Receptor Subtype ◽  
Lower Side ◽  
Prostanoid Receptor ◽  
Selective Agonists ◽  
Subtype Selective

Sa1746 A1 and A2A Adenosine Receptor Subtype Selective Agonists Activate Splanchnic Colonic Afferents With a Clear Modulatory Role of Nav1.9

2013 ◽  
Vol 144 (5) ◽  
pp. S-297
Author(s):  
Vincent Cibert-Goton ◽  
James R. Hockley ◽  
Michael Tranter ◽  
George Boundouki ◽  
Mark D. Baker ◽  
...  
Keyword(s):  
Adenosine Receptor ◽  
Receptor Subtype ◽  
A2a Adenosine Receptor ◽  
Selective Agonists ◽  
Subtype Selective

Synthesis and Sar of bulky 1-azabicyclo[2.2.1]-3-one oximes as muscarinic receptor subtype selective agonists

Life Sciences ◽  
1993 ◽  
Vol 52 (5-6) ◽  
pp. 505-511 ◽  
Author(s):  
H. Tecle ◽  
D.J. Lauffer ◽  
T. Mirzadegan ◽  
W.H. Moos ◽  
D.W. Moreland ◽  
...  
Keyword(s):  
Muscarinic Receptor ◽  
Receptor Subtype ◽  
Muscarinic Receptor Subtype ◽  
Selective Agonists ◽  
Subtype Selective

Decreased MAPK- and PGE2-dependent IL-11 production in Giα2−/− colonic myofibroblasts

2007 ◽  
Vol 292 (6) ◽  
pp. G1511-G1519 ◽  
Author(s):  
Brian Hoang ◽  
Alice Trinh ◽  
Robert A. Edwards
Keyword(s):  
Ex Vivo ◽  
Primary Cultures ◽  
Physiological Role ◽  
Mapk Signaling ◽  
Receptor Subtype ◽  
Selective Agonists ◽  
G Protein Alpha Subunit ◽  
Subtype Selective ◽  
Camp Levels ◽  
Protein Alpha Subunit

Mice deficient in the G-protein alpha subunit Giα2 spontaneously develop colitis and colon cancer. IL-11 is a pleiotropic cytokine known to protect the intestinal epithelium from injury in animal models of colitis and is produced by subepithelial myofibroblasts in response to inflammatory mediators including TGF-β, IL-1β, and PGE2. Arachidonic acid release and subsequent PGE2 production is significantly decreased in the colonic mucosa of Giα2−/− mice, and we hypothesized that this would affect mucosal IL-11 production. Mucosal levels of IL-11 were found to be significantly decreased in Giα2−/− mice despite the presence of mild colitis. Primary cultures of Giα2−/− intestinal and colonic myofibroblasts (IMF and CMF, respectively) produced less basal and TGF-β or IL-1β-stimulated IL-11 mRNA and protein than wild-type cells. Inhibitors of ERK or p38 MAPK activation dose dependently inhibited IMF and CMF IL-11 production in response to TGF-β stimulation, whereas 16,16 dimethyl-PGE2 and prostanoid receptor subtype-selective agonists induced IL-11 production. Treatment of animals with the EP4-specific agonist ONO-AE1-329 resulted in enhanced mucosal levels of IL-11, and increased IL-11 production by ex vivo cultured CMF. Modulation of cAMP levels produced diverging results, with enhancement of TGF-β-induced IL-11 release in IMF pretreated with 8-Br-cAMP and inhibition in cells treated either with pertussis toxin or the PKA inhibitor H-89. These data suggest a physiological role for prostaglandins, MAPK signaling, and cAMP signaling for the production of myofibroblast-derived IL-11 in the mouse intestinal mucosa.

Alpha-2 adrenergic agonism stimulates islet glucagon release from perfused rat pancreas: possible involvement of alpha-2A adrenergic receptor subtype

1992 ◽  
Vol 127 (3) ◽  
pp. 279-283 ◽  
Author(s):  
Hiroshi Hirose ◽  
Hiroshi Maruyama ◽  
Katsuhiko Itoh ◽  
Kazunori Koyama ◽  
Koichi Kido ◽  
...  
Keyword(s):  
Insulin Release ◽  
Adrenergic Receptor ◽  
Receptor Subtype ◽  
Glucagon Release ◽  
Perfused Rat Pancreas ◽  
Rat Pancreas ◽  
Selective Antagonist ◽  
Alpha Adrenoceptor ◽  
Selective Agonists ◽  
Subtype Selective

Although insulin release is known to be inhibited by alpha-2 adrenergic agonism, the effect of alpha adrenergic agonism on islet glucagon release remains controversial. Alpha-2 adrenoceptors are subdivided into alpha-2A and alpha-2B subtypes using receptor binding methods or cloning methodology. This study was designed to confirm the involvement of the alpha-2 adrenoceptor and its subtypes in glucagon release from the isolated, perfused rat pancreas. Both the alpha-2A preferential agonist oxymetazoline and the non-subtype-selective alpha-2 agonist clonidine induced concentration-dependent stimulation of glucagon release, starting at 10−8 and 10−7 mol/l, respectively (p<0.01). In contrast, neither of the two alpha-1 selective agonists, methoxamine and phenylephrine, at concentrations up to 10−6 mol/l affected glucagon release. Furthermore, the non-subtype-selective alpha-2 antagonist rauwolscine at concentrations of 10−6 and 10−5 mol/l and the alpha-1 and alpha-2A selective antagonist WB-4101 at 10−5 mol/l showed significant antagonism of 10−7 mol/l clonidine-induced glucagon release versus corresponding controls. Neither the alpha-1 and alpha-2B selective antagonist prazosin nor the alpha-2B preferential antagonist chlorpromazine, at concentrations up to 10−5 mol/l, antagonized the effects of clonidine. None of the eight drugs, at the concentrations tested, affected insulin release with 5.5 mmol/l glucose. These results suggest that in rats islet glucagon release induced by alpha adrenoceptor agonism is mediated through alpha-2 adrenoceptors, possibly the alpha-2A subtype.

Relaxations to oestrogen receptor subtype selective agonists in rat and mouse arteries

2005 ◽  
Vol 513 (1-2) ◽  
pp. 101-108 ◽  
Author(s):  
Khalid Al Zubair ◽  
Adibah Razak ◽  
Sotiria Bexis ◽  
James R. Docherty
Keyword(s):  
Oestrogen Receptor ◽  
Receptor Subtype ◽  
Selective Agonists ◽  
Subtype Selective
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