Pancreastatin (33–49) enhances the priming effect of glucose in the rat pancreas

Sánchez-Margalet, Vı́ctor; Goberna, R.

doi:10.1007/bf01955161

Cited by 6 publications

(1 citation statement)

References 16 publications

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“…[11][12][13][14] The role of PST as a regulatory enteropancreatic peptide has been established in the light of a variety of biologic effects in a number of tissues, which could be assigned to the carboxyl-terminal part of the molecule (see Sánchez-Margalet et al 15 for review). These effects are exerted on endocrine and exocrine pancreatic secretion, [16][17][18][19][20][21] gastric secretion, 22,23 parathormone release, 24 plasma catecholamine levels, 25 and memory retention. 26 Synthetic rat pancreastatin has also been shown to have biologic activity in various tissues.…”

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confidence: 99%

Pancreastatin receptor is coupled to a guanosine triphosphate-binding protein of the Gg/11α family in rat liver membranes

1998

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Pancreastatin (PST), a recently discovered regulatory peptide derived from chromogranin A, has been shown to have a glycogenolytic effect in the hepatocyte that is mediated by increasing intracellular calcium. Our previous studies on pancreastatin signaling suggested that PST receptor is coupled to some G proteins in the plasma membrane of the hepatocyte. The nature of this interaction was investigated using antisera against G q/11 ␣ by different approaches. Indirect evidence of a pertussis toxin (PT)-insensitive G protein of the family of G q/11 ␣ was obtained by measuring high-affinity guanosine triphosphatase (GTPase) activity in soluble rat liver membranes. PST increased GTPase activity in a dose-dependent manner. This effect was only slightly inhibited by PT pretreatment of the membranes, whereas anti-G q/11 ␣ antisera blocked most of the PST-stimulated GTPase activity. The selective association of the PST receptor with this G protein was further studied by the coelution in wheat germ agglutinin semipurification of the receptor and by immunoprecipitation of the G protein-PST receptor complexes using G-proteinspecific antisera. A G protein of the family of G q/11 ␣ was found to be associated with the semipurified PST receptor. Moreover, anti-G q/11 ␣ antisera immunoprecipitated most PST-binding activity (95%), bringing down most of the specific G protein, whereas anti-G i1,2 ␣ and -G o,i3 ␣ failed to immunoprecipitate the PST-binding activity. Finally, the coupling of the PST receptor with the effector phospholipase C was disrupted by blocking with G q/11 ␣ antisera, suggesting that a G protein of the family of G q/11 ␣ is a signal mediator from PST receptors to phospholipase C activation in rat liver membranes. (HEPATOLOGY 1998;27:608-614.) Pancreastatin (PST), a 49-amino acid peptide isolated from porcine pancreas, 1 arises from proteolytic cleavage of its precursor, chromogranin A (CGA), a glycoprotein present in endocrine and neuronal cells. [2][3][4][5] In islets, PST appears to be localized to the insulin-containing ␤ cells, somatostatincontaining ␦ cells, 6 and glucagon-containing ␣ cells. 7,8 On the other hand, postsecretory processing of CGA also occurs. 9,10 Rat CGA cDNA revealed the existence of a pancreastatin-like sequence, homologous to porcine pancreastatin. [11][12][13][14] The role of PST as a regulatory enteropancreatic peptide has been established in the light of a variety of biologic effects in a number of tissues, which could be assigned to the carboxyl-terminal part of the molecule (see Sánchez-Margalet et al. 15 for review). These effects are exerted on endocrine and exocrine pancreatic secretion, 16-21 gastric secretion, 22,23 parathormone release, 24 plasma catecholamine levels, 25 and memory retention. 26 Synthetic rat pancreastatin has also been shown to have biologic activity in various tissues. [27][28][29] In rat liver, we have previously shown that PST has a calcium-dependent glycogenolytic effect, [30][31][32][33] and an inhibitory effect on the insulin stimulation of glycogen...

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Pancreastatin receptor is coupled to a guanosine triphosphate-binding protein of the Gg/11α family in rat liver membranes

1998

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G protein G?q/11 and G?i1,2 are activated by pancreastatin receptors in rat liver: Studies with GTP-?35S and azido-GTP-?-32P

Santos‐Álvarez

Sánchez‐Margalet

1999

J. Cell. Biochem.

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In the liver, pancreastatin exerts a glycogenolytic effect through interaction with specific receptors, followed by activation of phospholipase C and guanylate cyclase. Pancreastatin receptor seems to be coupled to two different G protein systems: a pertussis toxin-insensitive G protein that mediates activation of phospholipase C, and a pertussis toxin sensitive G protein that mediates the cyclic GMP production. The aim of this study was to identify the specific G protein subtypes coupling pancreastatin receptors in rat liver membranes. GTP binding was determined by using gamma-35S-GTP; specific anti-G protein alpha subtype sera were used to block the effect of pancreastatin receptor activation. Activation of G proteins was demonstrated by the incorporation of the photoreactive GTP analogue 8-azido-alpha-32P-GTP into liver membranes and into specific immunoprecipitates of different Galpha subunits from soluble rat liver membranes. Pancreastatin stimulation of rat liver membranes increases the binding of gamma-35S-GTP in a time- and dose-dependent manner. Activation of the soluble receptors still led to the pancreastatin dose-dependent stimulation of gamma-35S-GTP binding. Besides, WGA semipurified receptors also stimulates GTP binding. The binding was inhibited by treatment with anti-Galphaq/11 (85%) and anti-Galphai1,2 (15%) sera, whereas anti-Galphao,i3 serum failed to affect the binding. Finally, pancreastatin stimulates GTP photolabeling of particulate membranes. Moreover, it specifically increased the incorporation of 8-azido-alpha-32P-GTP into Galphaq/11 and Galpha, but not into Galphao,i3 from soluble rat liver membranes. In conclusion, pancreastatin stimulation of rat liver membranes led to the activation of Galphaq/11 and Galphai1,2 proteins. These results suggest that Galphaq/11 and Galphai1,2 may play a functional role in the signaling of pancreastatin receptor by mediating the production of IP3 and cGMP respectively.

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Pancreastatin

Sánchez-Margalet

González-Yanes

Santos‐Álvarez

et al.

Advances in Experimental Medicine and Biology

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Pancreastatin (33–49) enhances the priming effect of glucose in the rat pancreas

Cited by 6 publications

References 16 publications

Pancreastatin receptor is coupled to a guanosine triphosphate-binding protein of the Gg/11α family in rat liver membranes

Pancreastatin receptor is coupled to a guanosine triphosphate-binding protein of the Gg/11α family in rat liver membranes

G protein G?q/11 and G?i1,2 are activated by pancreastatin receptors in rat liver: Studies with GTP-?35S and azido-GTP-?-32P

Pancreastatin

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