Effects of H1-receptor antagonists on 14C-aminopyrine accumulated in histamine-stimulated rabbit gastric glands.
After stimulation of gastric acid production there is a considerable delay before the acid starts to appear in the gastric lumen. The present study was carried out on isolated gastric glands to test the hypothesis that there may be a mechanism in the parietal cell that contributes to this delay by preventing emptying of the secretory canaliculi. Glands were incubated with 14C-aminopyrine and stimulated with histamine. After accumulation of 14C-aminopyrine various concentrations of H1-receptor antagonists were added. Clemastine, promethazine, and hydroxyzine effectively and cetirizine and tripelennamine less effectively decreased the accumulated 14C-aminopyrine content in a dose-dependent manner without significantly reducing the oxygen consumption. The H1-receptor antagonists influenced the 14C-aminopyrine content in another manner than H2-receptor antagonists. No effects were obtained by atropine or lidocaine, indicating that the elimination of 14C-aminopyrine is not an anticholinergic effect or due to membrane effects as exerted by local anesthetics. Stimulation of glands by further addition of histamine did not significantly stimulate the uptake of 14C-aminopyrine in the glands, whereas stimulation with db-cAMP produced an increase that was most pronounced when low concentrations of hydroxyzine had been used. It is suggested that H1-receptor antagonists do not inhibit stimulation of acid production in the secretory canaliculi. They may, however, interfere with a mechanism preventing acid from leaving the parietal cell. Such a mechanism may contribute to the delay in appearance of acid in the gastric lumen after stimulation of gastric acid production.
Nilsson
G
G
Dept. of Physiology, Swedish University of Agricultural Sciences, College of Veterinary Medicine, Uppsala.
Romell
B
B
Girma
K
K
Seensalu
R
R
D000632:Aminopyrine / Q000378:metabolism*; D000818:Animals; D002250:Carbon Radioisotopes; D004305:Dose-Response Relationship, Drug; D005746:Gastric Emptying / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D066298:In Vitro Techniques; D010101:Oxygen Consumption / Q000187:drug effects; D010295:Parietal Cells, Gastric / Q000187:drug effects*; D011817:Rabbits
D002250:Carbon Radioisotopes; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D000632:Aminopyrine; D006632:Histamine