Localization and function of adenosine receptor subtypes at the longitudinal muscle – Myenteric plexus of the rat ileum

2011 ◽  
Vol 59 (7) ◽  
pp. 1043-1055 ◽  
Author(s):  
Cátia Vieira ◽  
Fátima Ferreirinha ◽  
Isabel Silva ◽  
Margarida Duarte-Araújo ◽  
Paulo Correia-de-Sá
Author(s):  
Xue Yang ◽  
Laura H. Heitman ◽  
Adriaan P. IJzerman ◽  
Daan van der Es

AbstractAdenosine receptors, G protein–coupled receptors (GPCRs) that are activated by the endogenous ligand adenosine, have been considered potential therapeutic targets in several disorders. To date however, only very few adenosine receptor modulators have made it to the market. Increased understanding of these receptors is required to improve the success rate of adenosine receptor drug discovery. To improve our understanding of receptor structure and function, over the past decades, a diverse array of molecular probes has been developed and applied. These probes, including radioactive or fluorescent moieties, have proven invaluable in GPCR research in general. Specifically for adenosine receptors, the development and application of covalent or reversible probes, whether radiolabeled or fluorescent, have been instrumental in the discovery of new chemical entities, the characterization and interrogation of adenosine receptor subtypes, and the study of adenosine receptor behavior in physiological and pathophysiological conditions. This review summarizes these applications, and also serves as an invitation to walk another mile to further improve probe characteristics and develop additional tags that allow the investigation of adenosine receptors and other GPCRs in even finer detail.


2010 ◽  
Vol 34 (8) ◽  
pp. S19-S19
Author(s):  
Jun‑Ping Li ◽  
Chang‑Jun Gao ◽  
Bo‑Chang Lü ◽  
Ting Zhang ◽  
Jiang‑Bo Ma ◽  
...  

Endocrinology ◽  
1999 ◽  
Vol 140 (9) ◽  
pp. 4320-4334 ◽  
Author(s):  
S. Chidananda Sharma ◽  
Jeffrey W. Clemens ◽  
Margareta D. Pisarska ◽  
JoAnne S. Richards

Author(s):  
Daniel E Levin ◽  
Arabinda Mandal ◽  
Mark A Fleming ◽  
Katherine H Bae ◽  
Brielle Gerry ◽  
...  

Abstract The role of enteric neurons in driving intestinal peristalsis has been known for over a century. However, in recent decades, scientists have begun to unravel additional complex interactions between this nerve plexus and other cell populations in the intestine. Investigations into these potential interactions is complicated by a paucity of tractable models of these cellular relationships. Here, we describe a novel technique for ex vivo coculture of enteroids, so called “mini-guts,” in juxtaposition to the longitudinal muscle myenteric plexus (LMMP). Key to this system, we developed a LMMP culture media that: 1) allows the LMMP to maintain ex vivo peristalsis for 2 weeks along with proliferation of neurons, glia, smooth muscle and fibroblast cells, and 2) supports the proliferation and differentiation of the intestinal stem cells into enteroids complete with epithelial enterocytes, Paneth cells, goblet cells and enteroendocrine cells. Importantly, this technique identifies a culture condition that supports both the metabolic needs of intestinal epithelium as well as neuronal elements, demonstrating the feasibility of maintaining these two populations in a single culture system. This sets the stage for experiments to better define the regulatory interactions of these two important intestinal cell populations.


1997 ◽  
Vol 357 (1) ◽  
pp. 1-9 ◽  
Author(s):  
K.-N. Klotz ◽  
J. Hessling ◽  
J. Hegler ◽  
C. Owman ◽  
B. Kull ◽  
...  

2006 ◽  
Vol 51 (3) ◽  
pp. 397-413 ◽  
Author(s):  
Patricia C. Brum ◽  
Carl M. Hurt ◽  
Olga G. Shcherbakova ◽  
Brian Kobilka ◽  
Timothy Angelotti

1991 ◽  
Vol 261 (4) ◽  
pp. G693-G700 ◽  
Author(s):  
J. W. Wiley ◽  
Y. X. Lu ◽  
C. Owyang

The objective of this study was to determine whether L-glutamate (L-Glu) may serve as a neurotransmitter candidate in the guinea pig myenteric plexus. We observed that [3H]Glu and gamma-[3H]aminobutyric acid were synthesized from [3H]glutamine and released from neurons of the myenteric plexus during K+ and 1,1-dimethyl-4-phenylpiperazinium-evoked depolarization in a concentration-dependent manner. Muscle tension studies performed on ileal longitudinal muscle-myenteric plexus (LM-MP) preparations revealed that L-Glu [mean effective dose (ED50) 2.5 x 10(-5) M] produced concentration-dependent contractions, which were unaffected by hexamethonium but abolished by tetrodotoxin, atropine, and magnesium, suggesting that L-Glu acts via N-methyl-D-aspartate (NMDA)-type receptors that stimulate a cholinergic neural pathway unaffected by ganglionic blockade. In addition, L-Glu (ED50 4 x 10(-5) M) and NMDA (ED50 2 x 10(-4) M) stimulated concentration-dependent release of [3H]acetylcholine (ACh) from LM-MP sections, which was inhibited by tetrodotoxin, magnesium, and the NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid (AP-5). L-Glu-mediated release of [3H]ACh was enhanced by theophylline (10-6 M) and 3-isobutyl-1-methylxanthine (1 mM) and was significantly reduced by the adenylate cyclase inhibitor, 2',5'-dideoxyadenosine (10(-4) M) and somatostatin-14 (10(-6) M), which inhibits adenosine 3',5'-cyclic monophosphate (cAMP)-dependent cholinergic transmission in the myenteric plexus. These studies suggest that L-Glu may serve as an excitatory neurotransmitter in the myenteric plexus via its action on NMDA-type receptors, which are coupled to cAMP-dependent release of ACh.


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