Mechanism for increase of gastrin release by secretin in Zollinger-Ellison syndrome.
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.
Chiba
T
T
Third Department of Internal Medicine, Kobe University School of Medicine, Japan.
Yamatani
T
T
Yamaguchi
A
A
Morishita
T
T
Nakamura
A
A
Kadowaki
S
S
Fujita
T
T
D000262:Adenylyl Cyclases / Q000378:metabolism; D005260:Female; D005755:Gastrins / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000096:biosynthesis; D008875:Middle Aged; D012633:Secretin / Q000494:pharmacology*; D013004:Somatostatin / Q000494:pharmacology; D015043:Zollinger-Ellison Syndrome / Q000378:metabolism*
D005755:Gastrins; D007295:Inositol Phosphates; D012633:Secretin; D013004:Somatostatin; D006160:Guanosine Triphosphate; D000262:Adenylyl Cyclases