Body temperature-dependent action of baclofen in rat stomach. Relation to acid secretion and ulcerogenicity.
The effect of baclofen (PCPGABA) on acid secretion, motility, and mucosa was investigated in the anesthetized rat stomach under various body temperatures (BT: 28-38 degrees C), and they were compared with those of 2-deoxy-D-glucose (2DG), an acid stimulant through cytoglycopenia. Under these conditions PCPGABA induces lesions dose-dependently (greater than 1 mg/kg, subcutaneously) in both the stomach and duodenum, and this action was dependent on BT; lowering of BT enhanced the ulcerogenicity. PCPGABA (3 mg/kg) had no effect on acid secretion at higher BT (36-38 degrees C) but produced a marked increase of acid output at lower BT (30-32 degrees C). 2DG caused a stimulation of acid output and gastric lesions without BT dependency, but the duodenal ulcerogenicity enhanced at lower BT. Gastric motility was enhanced significantly by these two agents to similar degrees, at either high or low BT. Neither PCPGABA nor 2DG affected alkaline secretion in the duodenum, while lowering of BT by itself reduced alkaline secretory responses. The above changes caused by PCPGABA and 2DG were blocked by both atropine and vagotomy. These results suggest that (1) acid stimulatory and ulcerogenic action of PCPGABA may involve a temperature-dependent process but does not relate to a cytoglycopenia, and (2) the vagus nerve mediating acid secretion and motility may be different in the temperature dependency.
Takeuchi
K
K
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Nishiwaki
H
H
Niida
H
H
Okabe
S
S
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001418:Baclofen / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects* / Q000502:physiology; D003847:Deoxyglucose / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000187:drug effects* / Q000502:physiology; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000503:physiopathology; D014628:Vagotomy
D001285:Atropine; D003847:Deoxyglucose; D001418:Baclofen