Mechanism of action of SCN in isolated gastric glands.
Isolated gastric glands were used to study the mechanism of acid secretory inhibition by thiocyanate (SCN). It was found that SCN does not act as a competitive antagonist of histamine nor does SCN prevent the increase in cellular cAMP associated with histamine stimulation. SCN modifies but does not prevent the expansion of parietal cell canaliculi, indicating that this characteristic morphological transition does not require the actual formation of hydrochloric acid. Low doses (less than 5 mM) of SCN were found to inhibit aminopyrine accumulation, an index of acid formation, but do not inhibit either resting or stimulated respiration. Higher doses (greater than 10 mM) of SCN produce significant inhibition of stimulated but not resting respiration. These results indicate that SCN has two actions, i.e., inhibition of acid formation that requires low doses and inhibition of oxidative metabolism that requires higher doses. Incubation of glands in high-K+ (108 mM) medium leads to formation of an acid gradient in the absence of other secretagogues. The gradient was found to be transient, and its formation does not require oxidative metabolism, indicating that continued proton pumping is not required. Low doses of SCN were found to be more effective in dissipating the high-K+-induced gradient than a similar gradient induced by histamine stimulation. These results support the hypothesis that SCN inhibits acid secretion by increasing the rate of proton-gradient dissipation rather than interfering with a proton-pump mechanism.
D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D003864:Depression, Chemical; D005750:Gastric Juice / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D010101:Oxygen Consumption; D011817:Rabbits; D013861:Thiocyanates / Q000494:pharmacology*
D013861:Thiocyanates; D000632:Aminopyrine; D006632:Histamine; D000242:Cyclic AMP