Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An intraperitoneal (i.p.) injection of pentagastrin (250 micrograms/kg, three times daily) for 1 week increased somatostatin like-immunoreactivity (SSLI) content in the pancreas and the number of somatostatin (SS) receptors in pancreatic acinar membranes without influencing their apparent affinity as compared with control animals. No significant differences were seen in basal or forskolin (FK)-stimulated adenylate cyclase (AC) enzyme activities in the control and pentagastrin treated rats. In spite of the increase in the number of SS receptors, SS caused a significantly lower inhibition in AC activity in these membranes. This finding is related to the fact that the stable GTP analogue, 5'-guanylylimidodiphosphate (Gpp[NH]p) was a much less potent inhibitor of binding in the pancreatic acinar cell membranes from pentagastrin-treated animals than in those from controls. In addition the ability of Gpp(NH)p to inhibit FK-stimulated AC activity was also decreased in pancreatic acinar cell membranes from pentagastrin-treated rats. Pretreatment with proglumide, (20 mg/kg i.p.) a gastrin/cholecystokinin (CCK) receptor antagonist, prevented the pentagastrin-induced changes in SS level and binding as well as the inhibitory effect of SS on AC activity in pancreatic acinar cell membranes. Proglumide alone had no observable effect on the somatostatinergic system. These data suggest a SS receptor/G protein uncoupling as a result of binding of pentagastrin to gastrin receptors present in pancreatic acinar cell membranes.
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PMID:The effect of pentagastrin on the somatostatin receptor/effector system in rat pancreatic acinar membranes. 771 80

The mechanism whereby somatostatin (SS) produces beneficial effects in established pancreatitis induced by pancreaticobiliary duct ligation (PBDL) is still not clear. The aim of the work was to evaluate the possibility of a direct action of SS on pancreatic acinar cells from rats with acute pancreatitis. For this purpose, we studied the SS-receptor-adenylate cyclase system in pancreatic acinar membranes from both, control rats and rats with experimentally induced acute pancreatitis. On the other hand, it has been reported that cholecystokinin (CCK) diminishes the number of SS receptors in pancreatic acinar cells. Proglumide, a CCK receptor antagonist reduces the severity of acute pancreatitis in the rat. Therefore, we have also examined the effect of proglumide on the somatostatinergic system in controls and rats with acute pancreatitis. Fourteen hours after PBDL, the SS receptors, the capacity of the SS analogue SMS 201-995 to inhibit forskolin-stimulated adenylate cyclase activity and PTX-catalyzed [32P] ADP-ribosylation of the alpha1 subunits of Gi proteins could not be detected in pancreatic acinar membranes. One month after reopening the closed pancreaticobiliary duct (PBD), the pancreas showed regeneration of acinar cells, and the above-mentioned parameters were significantly lower than in the control group. Two months after reopening the closed PBD, all these parameters had returned to control values. The administration of proglumide (20 mg/kg i.p.), a cholecystokinin receptor antagonist, accelerated pancreatic regeneration and approached all these parameters to control values one month after reopening the closed PBD. The present study suggests that the beneficial effects of SS on established pancreatitis induced by PBDL may not be due to a direct action of the peptide on pancreatic acinar cells at least at 14 hours after PBDL. In addition, these findings suggest that in established pancreatitis the effect of proglumide on the SS receptor-adenylate cyclase system could be due to its action on pancreatic regeneration.
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PMID:The somatostatin receptor-adenylate cyclase system in rat pancreatic acinar membranes after temporary pancreaticobiliary duct ligation. 940 49