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Five healthy adult men were given metoclopramide (10 and 20 mg) iv, and in repeated tests almost always developed transient restlessness lasting from 10-30 min. The effects of L-dopa and dexamethasone on metoclopramide-induced increases in cortisol concentration were determined. These response values were compared with those of a control. After an injection of 10 mg metoclopramide, the cortisol level increased significantly only at 40 min; the ACTH level did not change. The cortisol rise was suppressed by dexamethasone pretreatment. Pretreatment with 0.5 g L-dopa resulted in a decrease in the PRL level from -20 min to 20 min, and the increase in cortisol seen at 40 min was cancelled. The ACTH level did not change. After injecting 20 mg metoclopramide, the ACTH level increased significantly from 20 min to 60 min and the cortisol level showed a significant increase from 20 min to 120 min. Pretreatment with dexamethasone resulted in a decrease in these hormones. The L-dopa pretreatment did not reduce even the rise in the PRL level which resulted from the administration of 20 mg metoclopramide. These findings suggest that the ACTH and cortisol response to metoclopramide is a stress-mediated effect. Plasma cortisol responses to 20 mg metoclopramide and insulin-induced hypoglycemia were studied and compared in seven volunteers and found to be similar.

Five healthy adult men were given metoclopramide (10 and 20 mg) iv and the effects of L-dopa and dexamethasone on metoclopramide-induced increases in plasma aldosterone concentration were determined. Plasma PRL, ACTH, and cortisol levels were also measured and the results reported in a previous study. After an injection of 10 mg metoclopramide, aldosterone levels increased significantly. The aldosterone rise was inhibited by L-dopa, but not by dexamethasone. After injecting 20 mg metoclopramide, aldosterone levels increased significantly vs. both the control and the basal level. The aldosterone increase was not inhibited by L-dopa pretreatment, whereas pretreatment with dexamethasone did suppress it. The data suggest that metoclopramide increased aldosterone secretion through an ACTH-dependent (stress mediated) effect in addition to its antidopaminergic adrenal action, simultaneously. There were no significant differences between the ACTH-dependent and dopamine antagonist-mediated aldosterone increases in either the 10- or 20-mg tests. However, the ACTH-dependent aldosterone increase was statistically greater in the 20-mg test than in the 10-mg test, whereas there was only a slight and not statistically significant difference in the dopamine antagonist-mediated aldosterone increase between the tests. This means that the ACTH-dependent component of the aldosterone secretion is affected by the doubling of the metoclopramide dose, whereas the dopamine antagonist-mediated component is not.

Somatostatin (SRIF)-like immunoreactivity (SLI) in the thyroid glands of human and several animal species were compared, and the SLI peptides were characterized chromatographically and immunologically. All specimens were extracted with 2 M acetic acid, and the SLI content determined by RIA. The SLI concentrations in guinea pigs [34.3 +/- (SE) 4.8 ng/mg protein] and rabbits (9.4 +/- 0.8 ng/mg protein) were much greater than those in other mammals: dogs, rats, mice, and humans. On gel filtration of extracts of the guinea pig, rabbit and dog thyroids, the major peak of SLI (1.6 K SLI) coeluted with synthetic SRIF-14 (S-14). Two other forms of SLI ("big" SLI and 3 K SLI) were also detected, although their relative proportions to total SLI were small (2.3 to 8.2%). The 3 K SLI and 1.6 K SLI from guinea pig and rabbit thyroids contained peptides coeluting with synthetic SRIF-28 (S-28) and S-14, respectively, on reverse-phase high performance liquid chromatography. The dilution curves of the two molecular forms of SLI, i.e. 3 K SLI and 1.6 K SLI, were parallel to the displacement curves of S-28 and S-14 in the SRIF RIA. It is concluded 1) that the thyroid contents of SLI varied greatly from species to species, with the highest content being found in guinea pig thyroids; 2) that in guinea pigs, rabbits, and dogs, the predominant form of thyroid SLI is 1.6 K SLI; and 3) that the 3 K SLI and 1.6 K SLI peptides from guinea pig and rabbit thyroids are immunologically and chromatographically indistinguishable from S-28 and S-14, respectively.

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