Kawashima Hiroyuki

Characterization of cloned human cholecystokinin-B receptor as a gastrin receptor

Abstract The cholecystokinin (CCK)-B receptor cloned from human brain was characterized as a gastrin receptor by using heterologous expression systems of COS-7 cells and Xenopus oocytes. 125 I-gastrin binding to human CCK-B receptor expressed in COS-7 was time-dependent, saturable and also specific, as well as 125 -I-CCK-8. The binding of 125 I-gastrin was inhibited by CCK-8 about 10-fold more potently than by gastrin. The rank order of potency of several antagonists to 125 I-gastrin binding was YM022 > CI-988 > L-365,260 > L-364,718. Addition of GTP γS, a nonhydrolysable analog of GTP, dose-dependently inhibited 125 I-gastrin binding, and lowered the gastrin binding affinity, Gastrin (10 −9 –10 −7 M) also evoked a Ca 2+ -dependent Cl − current in Xenopus oocytes expressing CCK-B receptors. These results suggest that the pharmacological profile of the cloned human CCK-B receptor using 125 I-gastrin is closely parallel to that reported in gastric mucosa, and that the receptor transduces cellular signals of gastrin as well as those of CCK-8.

Aspirin inhibition of 1α-hydroxyvitamin D3 or parathyroid hormone induced hypercalcemia in vivo in rats: A mechanism independent of prostaglandin biosynthesis inhibition

The interactions of calcium-regulating hormones, active forms of vitamin D and parathyroid hormone, and aspirin were studied in rats. Aspirin, a prostaglandin biosynthesis inhibitor, abolished the hypercalcemia induced by 1α-hydroxyvitamin D3 at 20, 50 and 100 mg/kg p.o. in parathyroidectomized or thyroparathyroidectomized rats with or without vitamin D deficiency, and in thyroparathyroidectomized plus nephrectomized rats. Aspirin did not affect the stimulation of intestinal calcium absorption by 1α-hydroxyvitamin D3. By contrast, indomethacin, another prostaglandin biosynthesis inhibitor, did not affect hypercalcemia or stimulation of intestinal calcium absorption by 1α-hydroxyvitamin D3. Aspirin also abolished the hypercalcemie action of parathyroid hormone in rats with or without intact thyroparathyroid glands. Moreover, aspirin alone caused hypocalcemia in rats with intact thyroparathyroid glands. Indomethacin had no effect in either of these systems. These data suggest that aspirin may inhibit bone resorption by the active form of vitamin D or parathyroid hormone via a mechanism independent of prostaglandin biosynthesis inhibition.