Reciprocal effect of unsulfated and sulfated forms of cholecystokinin-octapeptide on gastric acid secretion in the rat.

The sulfated and unsulfated forms of cholecystokinin-octapeptide (CCK-8) were compared, with respect to their effect on gastric acid secretion, in the rat. Unsulfated CCK-8 stimulated acid secretion in a dose-dependent manner, while the sulfated form was without stimulatory effect; thus, sulfation of the tyrosine residue in the seventh position from the C terminus completely abolished the gastrin-like action of CCK-8. Compared with pentagastrin and human gastrin II, unsulfated CCK-8 gave lower calculated maximal response. While sulfated CCK-8 given alone had no effect on acid secretion, it caused marked inhibition of the plateau response to submaximal pentagastrin. This inhibition was surmountable with higher doses of pentagastrin, suggesting a competitive type of inhibition. It is, therefore, concluded that lack of sulfation of the tyrosine residue in the seventh position does not exclude CCK-8 from occupying the gastrin receptor; but does prevent the hormone-receptor interaction that leads to the secretory response. These observations in the rat are different from those in the dog where desulfation of tyrosine renders the CCK analog, caerulein, ineffective in its ability to stimulate acid secretion.