Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In patients with Zollinger-Ellison syndrome, serum gastrin level is increased by secretin and is decreased by somatostatin. To elucidate the cellular mechanism for these actions, we investigated the direct effects of secretin and somatostatin on dispersed gastrinoma cells from a patient with Zollinger-Ellison syndrome. In the presence of 3-isobutyl-1-methylxanthine, secretin significantly stimulated gastrin release from dispersed gastrinoma cells, which was inhibited by somatostatin. In the presence of guanosine 5'-triphosphate, furthermore, secretin enhanced adenylate cyclase activation in the membranes from these cells, and this activation was reduced by somatostatin, whereas neither secretin nor somatostatin affected inositol phospholipid turnover. On the other hand, removal of guanosine 5'-triphosphate from incubation medium abolished both the stimulatory effect of secretin and the inhibitory effect of somatostatin on adenylate cyclase activation. Furthermore, pertussis toxin pretreatment reversed the ability of somatostatin to inhibit secretin-induced increase in gastrin release and activation of adenylate cyclase. Thus, in this gastrinoma patient, secretin and somatostatin appeared to act directly on gastrinoma cells to stimulate and inhibit gastrin secretion, respectively, by modulating adenylate cyclase activation, probably via guanine nucleotide-binding proteins.
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PMID:Mechanism for increase of gastrin release by secretin in Zollinger-Ellison syndrome. 261 6

In the present study we investigated the effects of the somatostatin (SS) analogs octreotide, RC-160, and BIM-23014 on GH release by cultured cells of human GH-secreting pituitary tumors, in normal rat anterior pituitary cells, and on gastrin release by cultured cells from a human gastrinoma. In all GH-secreting adenomas and in rat anterior pituitary cells, RC-160 was the most potent compound. RC-160 significantly inhibited GH-, PRL, and/or alpha-subunit release by human GH-secreting pituitary adenoma cells in concentrations as low as 10(-12)-10(-14) M, whereas at the same concentrations, octreotide and BIM-23014 did not inhibit or were significantly less effective in inhibiting GH release (P < 0.01, RC-160 vs. octreotide and BIM-23014). In rat anterior pituitary cell cultures, the IC50 values for inhibition of GH release were, in rank order of potency, 0.1, 5.3, 47, 48, and 99 pM for RC-160, SS-14, BIM-23014, octreotide, and SS-28, respectively. Maximal inhibitory effects by the three analogs were the same in the human GH adenoma cell cultures and the rat anterior pituitary cell cultures (-60%). On the basis of these data, RC-160 appears to be about 500 times more potent than octreotide and BIM-23014 in inhibiting GH release by rat anterior pituitary cells in vitro. Forskolin (100 microM) as well as pretreatment of the cells with pertussis toxin significantly diminished the inhibitory effects of the three SS analogs and those of SS-14 and SS-28 to the same extent. The latter data suggest that octreotide, RC-160, and BIM-23014 act mainly via a pertussis toxin-sensitive G-protein and an adenylyl cyclase-dependent mechanism. In the human gastrinoma culture, RC-160 inhibited gastrin release significantly more than octreotide at 10(-12)- and 10(-14)-M concentrations (P < 0.01). In conclusion, the SS analogs octreotide, RC-160, and BIM-23014 may have significant different potencies of inhibition of hormone release in vitro, with RC-160 being the most potent SS analog and octreotide and BIM-23014 having similar potencies. Depending on the pharmacokinetic properties of these three octapeptide SS analogs, these observations may have consequences for the medical therapy of patients with SS receptor-positive endocrine tumors.
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PMID:Relative potencies of the somatostatin analogs octreotide, BIM-23014, and RC-160 on the inhibition of hormone release by cultured human endocrine tumor cells and normal rat anterior pituitary cells. 790 31