Effect on gastric secretion, gastrin and histamine release during and after long-term treatment by pirenzepine in dogs.
We assessed the effects of pirenzepine (2 mg/kg per os) on gastric secretion and gastrin and histamine release in response to food and histamine dihydrochloride infusion in four dogs during 24 weeks of treatment and for 15 weeks after the end of treatment. The results were compared to those obtained in the same animals in control experiments, before treatment, and in four untreated dogs. Pirenzepine absorption was checked by measuring plasma concentrations. Pirenzepine led to a significant reduction in acid and pepsin secretion in response to histamine. In response to food, the reduction in secretion was concomitant with a reduction in gastrin and histamine release. Baseline concentrations of gastrin were reduced, while those of histamine were unchanged. No side effects were observed. After treatment, a long time lapse (about 15 weeks) was required for acid and pepsin secretion and gastrinemia to return to control levels, while histamine release in response to food normalized rapidly. Pirenzepine fixes selectively to M1 muscarinic receptors of the synaptic ganglion, thus inhibiting the effect of vagal stimulation, especially on pepsin secretion. Our data suggest that it might also fix to M1 receptors located on ECL cells, thereby reducing histamine release. In addition, pirenzepine probably fixes to other muscarinic receptors inhibiting gastrin release and resulting in a G and secretory cell mass reduction, probably by increasing somatostatin release.
Vatier
J
J
Département de Pharmacie Clinique, Faculté de Pharmacie, Paris, France.
Riquet
W
W
Célice-Pingaud
C
C
Olivier
A
A
Mignon
M
M
Farinotti
R
R
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D004285:Dogs; D004435:Eating; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D005755:Gastrins / Q000378:metabolism; D006632:Histamine / Q000097:blood / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D008297:Male; D010434:Pepsin A / Q000378:metabolism; D010890:Pirenzepine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D011976:Receptors, Muscarinic / Q000378:metabolism
D000897:Anti-Ulcer Agents; D005755:Gastrins; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D006632:Histamine; D010434:Pepsin A