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C F Code

Publications and source records attributed to C F Code.

At least 55 records · Page 3Linked to original sources

Effect of histamine and its methyl derivatives on cyclic AMP metabolism in gastric mucosa and its blockade by an H2 receptor antagonist.

In a cell-free system prepared from guinea pig gastric mucosa, histamine and Nalpha-methyl-histamine produced dose-dependent stimulation of cyclic AMP formation and 1,4-methylhistamine had a minimal stimulatory effect. N-methyl-N'-(2-[5-methylimidazole-4-yl-methylthio]-ethyl) -thiourea (metiamide), a new H2 receptor inhibitor, selectively blocked the stimulation of adenylate cyclase by histamine and its active methyl derivative but had no substantial effect on the basal adenylate cyclase activity or adenylate cyclase stimulated by sodium fluoride. Metiamide inhibited the histamine stimulation of adenylate cyclase at 1/100 the concentration of the histamine. Histamine, its methyl derivatives, and metiamide did not influence the activity of cyclic AMP phosphodiesterase from gastric mucosa. Therefore, histamine stimulates gastric mucosal adenylate cyclase via interaction with the H2 receptor without influencing cyclic AMP breakdown, and N-methylation of histamine on the side chain preserves or even increases its stimulating ability. On the other hand, N-methylation in the ring nearly abolishes the ability of histamine to interact with the H2 receptor.

Adenylyl Cyclases↗

Methyl histamines and gastric secretion.

1. The previous findings that N-methylhistamine and N-dimethylhistamine are more potent stimulators of gastric secretion than histamine have been confirmed in dogs with Heidenhain pouches or gastric fistulas.2. In cats with gastric fistulas, doses of N-methylhistamine of 0.25 or 0.5 mumole/hr produced 1.4-1.6 times as much HCl as equimolar doses of histamine.3. The maximal HCl outputs of dogs with Heidenhain pouches to histamine, N-methylhistamine, and N-dimethylhistamine were not significantly different, though lesser doses of the N-methyl derivatives were required to produce the maxima. At the one-half maximal level, N-dimethylhistamine showed a twofold greater potency than histamine.4. When given slowly or quickly via arteries supplying blood to the stomach of dogs or cats with gastric fistulas or via the artery to a Heidenhain pouch in a dog, 0.1-1.0 mumole N-methylhistamine or N-dimethylhistamine produced 4.1-13.9 times as much HCl as equimolar doses of histamine.5. Injection of histamine or N-methylhistamine via the portal vein in two dogs with gastric pouches stimulated less secretion of HCl than injection of the same doses via a systemic vein.6. The results allow the conclusion that N-methylhistamine and N-dimethylhistamine are more potent stimulators of acid gastric secretion than histamine in dogs and cats, particularly when delivered directly via the arterial route to the gastric mucosa, and support the prospect that N-methylhistamine or N-dimethylhistamine or both are natural chemostimulators of the parietal cells.

Animals↗

Localization of the duodenal pacemaker and its role in the organization of duodenal myoelectric activity.

In two series of conscious healthy dogs, a study of duodenal electric activity was made to locate the pacemaker or site of the greatest intrinsic frequency of the pacesetter potential. In three dogs, an annular myotomy of the duodenum about 1 cm proximal (orad) to the biliary ampulla caused a reduction in the frequency of the pacesetter potential distal (caudad) to the conduction block and demonstrated that the pacemaker was not in the region of the ampulla, as had been suggested previously. Annular myotomy of the duodenum at increasing intervals distal to the pylorus in a second series of eight dogs showed that the pacemaker was present in the proximal 5 to 6 mm of duodenum. The greater frequency of the pacemaker was found to maintain constant distal conduction of the pacesetter potential. Distal conduction of the pacesetter potential was shown on occasion to be associated with the distal propagation of action potentials along the duodenum.

Action Potentials↗