Route Development and Multikilogram GMP Delivery of a Somatostatin Receptor Antagonist

2012 ◽  
Vol 16 (8) ◽  
pp. 1329-1337 ◽  
Author(s):  
Rebecca T. Ruck ◽  
Mark A. Huffman ◽  
Gavin W. Stewart ◽  
Ed Cleator ◽  
Wynne V. Kandur ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Somatostatin Receptor ◽  
Somatostatin Receptor Antagonist

Galanin potentiates supramaximal caerulein-stimulated pancreatic amylase secretion via its action on somatostatin secretion

2009 ◽  
Vol 297 (6) ◽  
pp. G1268-G1273 ◽  
Author(s):  
Savio G. Barreto ◽  
Colin J. Carati ◽  
Ann C. Schloithe ◽  
James Toouli ◽  
Gino T. P. Saccone
Keyword(s):  
Receptor Antagonist ◽  
Muscarinic Receptor ◽  
Mechanism Of Action ◽  
Somatostatin Receptor ◽  
Amylase Secretion ◽  
Pancreatic Amylase ◽  
Galanin Receptor ◽  
Insulin Dependent ◽  
Somatostatin Receptor Antagonist ◽  
Dependent Mechanism

Galanin inhibits pancreatic amylase secretion from mouse lobules induced by physiological concentrations of caerulein via an insulin-dependent mechanism. We aimed to determine the effect and elucidate the mechanism of action of exogenous galanin on pancreatic amylase secretion induced by supramaximal concentrations of caerulein. Amylase secretion from isolated murine pancreatic lobules was measured. Lobules were coincubated with galanin (10−12–10−7 M) and caerulein (10−7 M). Lobules were preincubated with atropine (10−5 M), tetrodotoxin (10−5 M), diazoxide (10−7 M), or the galanin antagonist galantide (10−12–10−7 M) for 30 min followed by incubation with caerulein alone, or combined with galanin (10−12 M). Lobules were also coincubated with combinations of galanin (10−12 M), caerulein, octreotide (10−12–10−7 M) or cyclo-(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr[BZL]), a somatostatin receptor antagonist (10−9 M). Amylase secretion was expressed as percent of total lobular amylase. Caerulein stimulated amylase secretion to 124% of control. Diazoxide pretreatment abolished the caerulein-stimulated amylase secretion, whereas atropine or tetrodotoxin caused a partial inhibition. Galanin (10−12–10−7 M) potentiated caerulein-stimulated amylase secretion to 160% of control. Preincubation with a combination of atropine and diazoxide abolished the potentiating effect of galanin, indicating muscarinic receptor and insulin mediation. Preincubation with galantide abolished the galanin effect, implying galanin receptor involvement. Coincubation with caerulein, galanin, and octreotide significantly reduced the potentiating effect galanin. However, coincubation with the somatostatin receptor antagonist, alone or in combination with galanin, significantly increased caerulein-stimulated amylase secretion to a level comparable to the galanin potentiation. Taken together, these data suggest that, at supramaximal caerulein concentrations, galanin acts via its receptors to further increase caerulein-stimulated amylase secretion by inhibiting the caerulein-induced release of somatostatin.

scholarly journals Kit Ligand and the Somatostatin Receptor Antagonist, BIM-23627, Stimulate in Vitro Resting Follicle Growth in the Neonatal Mouse Ovary

Endocrinology ◽  
2010 ◽  
Vol 151 (3) ◽  
pp. 1299-1309 ◽  
Author(s):  
Alain Gougeon ◽  
Aurélien Delangle ◽  
Nassim Arouche ◽  
Mats Stridsberg ◽  
Jean Pierre Gotteland ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Somatostatin Receptor ◽  
Neonatal Mouse ◽  
Follicle Growth ◽  
Mouse Ovary ◽  
Kit Ligand ◽  
Somatostatin Receptor Antagonist

Microinjection of exogenous somatostatin in the dorsal vagal complex inhibits pancreatic secretion via somatostatin receptor-2 in rats

2007 ◽  
Vol 292 (3) ◽  
pp. G746-G752 ◽  
Author(s):  
Zhuan Liao ◽  
Zhao-Shen Li ◽  
Yan Lu ◽  
Wei-Zhong Wang
Keyword(s):  
Pancreatic Secretion ◽  
Exocrine Pancreas ◽  
Feedback Inhibition ◽  
Somatostatin Receptor ◽  
Inhibitory Effect ◽  
Receptor Subtype ◽  
Dependent Manner ◽  
Dorsal Vagal Complex ◽  
Somatostatin Receptor Antagonist ◽  
Dose Dependent

Previous studies have suggested that somatostatin inhibits pancreatic secretion at a central vagal site, and the dorsal vagal complex (DVC) is involved in central feedback inhibition of the exocrine pancreas. The aim of this study was to investigate the effect of exogenous somatostatin in the DVC on pancreatic secretion and the somatostatin receptor subtype(s) responsible for the effect. The effects of somatostatin microinjected into the DVC on pancreatic secretion stimulated by cholecystokinin octapeptide (CCK-8) or 2-deoxy-d-glucose (2-DG) were examined in anesthetized rats. To investigate the somatostatin inhibitory action site, a somatostatin receptor antagonist [SRA; cyclo(7-aminoheptanoyl-Phe-d-Trp-Lys-Thr)] was microinjected into the DVC before intravenous infusion of somatostatin and CCK-8/2-DG. The effects of injection of a somatostatin receptor-2 agonist (seglitide) and combined injection of somatostatin and a somatostatin receptor-2 antagonist (CYN 154806) in the DVC on the pancreatic secretion were also investigated. Somatostatin injected into the DVC significantly inhibited pancreatic secretion evoked by CCK-8 or 2-DG in a dose-dependent manner. SRA injected into the DVC completely reversed the inhibitory effect of intravenous administration of somatostatin. Seglitide injected into the DVC also inhibited CCK-8/2-DG-induced pancreatic protein secretion. However, combined injection of somatostatin and CYN 154806 did not affect the CCK-8/2-DG-induced pancreatic secretion. Somatostatin in the DVC inhibits pancreatic secretion via somatostatin receptor-2, and the DVC is the action site of somatostatin for its inhibitory effect.

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