Mechanism of action of SCN in isolated gastric glands

Abstract

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.

Action of gastrin in guinea pig oxyntic cells. Studies using quantitative cytochemistry.

“…However, the mechanism of action of NaSCN is unclear. NaSCN may inhibit acid secretion by increasing the rate of proton-gradient dissipation (27), may restrict access of OH ions to the enzyme (8), or may have a direct inhibitory action on carbonic anhydrase (46). Our data suggests that gastrin acts via a receptor-mediated mechanism which is separate from that of histamine and acetylcholine on the oxyntic cell, as has been suggested by Soll al.…”

“…The cellular mechanisms whereby gastrin stimulates oxyntic HIP were further investigated using agents which inhibit carbonic anhydrase activity (acetazolamide), an inhibitor ofrespiration (NaSCN) (27), and a compound that neutralizes proton pump activity (H 149/ 94). Acetazolamide (10-5 M), NaSCN (l0-4 M), and Hassle compound (H 149/94) (10-4 M) were added to a Dmax dose of gastrin (10-12 M).…”

Muscarinic responses of gastric parietal cells

“…Gastric glands were isolated from the gastric mucosa of New Zealand White rabbits as described previously IBerglindh el al., 1976: Chew el al., 1980: Hersey et al, 1981. In brief, lhe stomach was peal'used under pressure with phosphate buffered saline (PBS), removed, and rinsed with PBS.…”

Antisecretory actions of Baccharis trimera (Less.) DC aqueous extract and isolated compounds: Analysis of underlying mechanisms

“…The gland pellets were dried at 90 • C for 2 h, and after determination of their weights they were digested with 0.2 ml of 1 M NaOH at 90 • C, for 1 h. Samples of the supernatants and digested pellets were transferred to scintillation vials and the radioactivity was counted in a beta-counter (Packard Instruments). Nonspecific trapping of [ 14 C]-AP was determined in samples containing 10 mM NaSCN, an inhibitor of acid secretion (Hersey et al, 1981). Accumulation of [ 14 C]-AP in the gastric glands was determined as the ratio (R) of the trapped glandular radioactivity to the radioactivity of the incubation medium ).…”