The differential roles of sympathetic nerve activity in the pathogenesis of antral and corpus lesions induced by indomethacin in rats.
A s.c. dose (32 mg/kg) of indomethacin induced antral ulcers and corpus erosions in refed rats, but almost exclusively corpus erosions in fasted rats. In the refed rats the antral ulcers were not affected by a preganglionic splanchnicectomy, but were significantly attenuated by 6-hydroxydopamine (80 mg/kg i.p.), prazosin (32 mg/kg p.o.), yohimbine (32 mg/kg p.o.) or streptozotocin (80 mg/kg i.v.), whereas the corpus erosions were exaggerated by the latter three treatments. Blood analysis revealed that refeeding of fasted rats caused instant increases in plasma glucose and insulin levels and a subsequent gradual increase in plasma norepinephrine (NE). These plasma parameter changes were hardly affected by an indomethacin treatment. The NE response to refeeding was reversed by 6-hydroxydopamine which minimally affected the glucose and insulin responses. Splanchnicectomy changed none of these responses, although it almost completely depleted plasma epinephrine levels. The NE response was enhanced by yohimbine and prazosin, and the insulin response was enhanced by the former. Streptozotocin abolished the insulin response and reversed the NE response. It is concluded that hyperinsulinemia in response to refeeding induces NE release and results in an activation of alpha-1 and/or alpha-2 adrenergic receptors which plays a permissive role in the indomethacin-induced antral ulcer formation. Conversely, this series of events may play a protective role against the corpus erosion formation.
Basic Research Group, Tsukuba Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Ibaraki, Japan.
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K
Kuratani
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H
Kodama
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I
Yamaguchi
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002395:Catecholamines / Q000097:blood; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D007213:Indomethacin / Q000633:toxicity*; D007328:Insulin / Q000097:blood; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced*; D013311:Streptozocin / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D001786:Blood Glucose; D002395:Catecholamines; D007328:Insulin; D011453:Prostaglandins; D015016:Yohimbine; D013311:Streptozocin; D016627:Oxidopamine; D011224:Prazosin; D007213:Indomethacin