Mechanism of reserpine-induced acute gastric mucosal injury in the rat: role of endogenous 5-hydroxytryptamine.
1. Reserpine (5 mg/kg intraperitoneally) produced gastric mucosal vasoconstriction and injury in all rats within 6 h (injury score 38.8 +/- 2.1 mm2, mean +/- SEM). Coeliac ganglionectomy or the beta-adrenoceptor-blocking drug propranolol (5-15 mg/kg) did not influence these effects of reserpine, but vagotomy protected the rats against them. The alpha-adrenoceptor-blocking drugs phenoxybenzamine and phentolamine at 5 mg/kg were protective against injury. However, a 10 mg/kg dose of either blocker was more effective (2.2 +/- 0.5 mm2 and 3 +/- 0.8 mm2, respectively, versus 38.8 +/- 2.1 mm2, mean +/- SEM, P less than 0.01) and a dose of 15 mg/kg afforded complete protection. 2. Methysergide, a 5-hydroxytryptamine receptor antagonist, produced a dose-dependent increase in the reserpine-induced injury; a significant (P less than 0.05) increase was noted with 15 and 20 mg/kg (47.5 +/- 2.9 mm2 and 49.4 +/- 2.2 mm2, respectively, versus 38.8 +/- 2.1 mm2, mean +/- SEM). 3. The results suggest that, in the rat, reserpine causes vagal alpha-adrenoceptor stimulation producing gastric mucosal vasoconstriction and injury. 5-Hydroxytryptamine is not implicated in the mechanism of this injury and affords protection against it.
Salim
A S
AS
University Department of Surgery, Royal Infirmary, Glasgow, U.K.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D005728:Ganglia, Sympathetic / Q000502:physiology; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008784:Methysergide / Q000633:toxicity; D010643:Phenoxybenzamine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000633:toxicity*; D012701:Serotonin / Q000502:physiology*; D014628:Vagotomy
D010643:Phenoxybenzamine; D012701:Serotonin; D012110:Reserpine; D011433:Propranolol; D008784:Methysergide; D010646:Phentolamine