Effects of pirenzepine and atropine on vagal and cholinergic gastric secretion and gastrin release and on heart rate in the dog.
To characterize and quantitate pathways of stimulation of gastric secretion via vagal excitation induced by 2-deoxy-D-glucose, we used graded doses of the two muscarinic antagonists, atropine and pirenzepine. Studies were performed in four conscious gastric fistula dogs with antral vagotomy to eliminate the gastrin release component of the vagal response. To further localize the site of action of the antagonists, both were tested against bethanechol, which stimulates secretion at postganglionic sites. Acid and pepsin secretion stimulated by either bethanechol or the vagus were inhibited in a dose-responsive manner by both atropine and pirenzepine, which displayed similar potencies. These data indicate that: 1) the vagus acts on the gastric fundus solely via muscarinic receptors; 2) the muscarinic receptors controlling gastric secretion are of the high-affinity (M-1) subtype; and 3) the vagus is very sensitive to atropine with D50 less than 1.4 nmol/kg. Heart rate was increased up to 120 beats/min above the resting rate by atropine; half-maximal increase was calculated to occur at 10 nmol/kg (ED50). Pirenzepine had a much less potent effect on the heart; the ED50 was 200 to 300 times greater than that for atropine. These data indicate that heart rate is affected by a mechanism acting via a muscarinic receptor pathway that has a low affinity for pirenzepine (M-2 receptor subtype).
D000818:Animals; D001285:Atropine / Q000008:administration & dosage*; D001570:Benzodiazepinones / Q000008:administration & dosage*; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000008:administration & dosage; D002799:Cholinergic Fibers / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism*; D005755:Gastrins / Q000097:blood*; D006339:Heart Rate / Q000187:drug effects*; D010434:Pepsin A / Q000378:metabolism; D010890:Pirenzepine; D014630:Vagus Nerve / Q000187:drug effects
D001570:Benzodiazepinones; D001626:Bethanechol Compounds; D005755:Gastrins; D018723:Bethanechol; D010890:Pirenzepine; D001285:Atropine; D010434:Pepsin A