P2-065: IN VITRO PHARMACOLOGICAL CHARACTERIZATION OF S68890, AN ALLOSTERIC MODULATOR OF ALPHA7 NICOTINIC RECEPTORS

Background Functional α1- and α2-adrenoreceptor subtype pharmacology was characterized in an in vitro human nasal mucosa contractile bioassay. Methods Nasal mucosa was obtained from 49 donor patients and mucosal strips were placed in chambers filled with Krebs–Ringer solution and attached to isometric force transducers. Results Nonselective α-adrenoreceptor agonists epinephrine, norepinephrine, and oxymetazoline produced concentration-dependent contractions of isolated human nasal mucosa (pD2= 5.2, 4.9, and 6.5, respectively). The α2-adrenoreceptor agonist BHT-920 (10 μM)–induced contractions were blocked by yohimbine (0.01–1 μM) and prazosin (0.01–1 μM) inhibited the contractile response to the α1-adrenoreceptor agonist phenylephrine (10 μM). Histological analysis showed that phenylephrine and BHT-920 differentially contracted the arteries and veins of human nasal mucosa, respectively. Conclusion Our results indicate that functional α1- and α2-adrenoceptors are present and functional in human nasal mucosa. The a 2-adrenoceptors display a predominant role in contracting the veins and the α1-adrenoceptors appear to preferentially constrict the human nasal arteries.

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In Vitro Pharmacological Characterization of a Novel Selective α7 Neuronal Nicotinic Acetylcholine Receptor Agonist ABT-107

Journal of Pharmacology and Experimental Therapeutics ◽

10.1124/jpet.110.167072 ◽

2010 ◽

Vol 334 (3) ◽

pp. 863-874 ◽

Cited By ~ 40

Author(s):

John Malysz ◽

David J. Anderson ◽

Jens H. Grønlien ◽

Jianguo Ji ◽

William H. Bunnelle ◽

...

Keyword(s):

Acetylcholine Receptor ◽

Nicotinic Acetylcholine Receptor ◽

Receptor Agonist ◽

Neuronal Nicotinic Acetylcholine Receptor ◽

Pharmacological Characterization ◽

Nicotinic Acetylcholine

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In vitro and in vivo characterization of PheTQS, a novel α7 nAChR positive allosteric modulator

Biochemical Pharmacology ◽

10.1016/j.bcp.2009.06.064 ◽

2009 ◽

Vol 78 (7) ◽

pp. 913 ◽

Cited By ~ 1

Author(s):

James N.C. Kew ◽

Selina Mok ◽

Annette Weil ◽

Caterina Virginio ◽

Laura Castelletti ◽

...

Keyword(s):

Allosteric Modulator ◽

Positive Allosteric Modulator ◽

Α7 Nachr ◽

In Vivo Characterization

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Molecular and functional characterization of somatostatin-type signalling in a deuterostome invertebrate

Open Biology ◽

10.1098/rsob.200172 ◽

2020 ◽

Vol 10 (9) ◽

pp. 200172

Author(s):

Ya Zhang ◽

Luis Alfonso Yañez Guerra ◽

Michaela Egertová ◽

Cleidiane G. Zampronio ◽

Alexandra M. Jones ◽

...

Keyword(s):

Functional Characterization ◽

The Body ◽

Pharmacological Characterization ◽

Cardiac Stomach ◽

Physiological Processes ◽

Pharmacological Tests ◽

The Central Nervous System

Somatostatin (SS) and allatostatin-C (ASTC) are structurally and evolutionarily related neuropeptides that act as inhibitory regulators of physiological processes in mammals and insects, respectively. Here, we report the first molecular and functional characterization of SS/ASTC-type signalling in a deuterostome invertebrate—the starfish Asterias rubens (phylum Echinodermata). Two SS/ASTC-type precursors were identified in A. rubens (ArSSP1 and ArSSP2) and the structures of neuropeptides derived from these proteins (ArSS1 and ArSS2) were analysed using mass spectrometry. Pharmacological characterization of three cloned A. rubens SS/ASTC-type receptors (ArSSR1–3) revealed that ArSS2, but not ArSS1, acts as a ligand for all three receptors. Analysis of ArSS2 expression in A. rubens using mRNA in situ hybridization and immunohistochemistry revealed stained cells/fibres in the central nervous system, the digestive system (e.g. cardiac stomach) and the body wall and its appendages (e.g. tube feet). Furthermore, in vitro pharmacological tests revealed that ArSS2 causes dose-dependent relaxation of tube foot and cardiac stomach preparations, while injection of ArSS2 in vivo causes partial eversion of the cardiac stomach. Our findings provide new insights into the molecular evolution of SS/ASTC-type signalling in the animal kingdom and reveal an ancient role of SS-type neuropeptides as inhibitory regulators of muscle contractility.

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