Gastroprotective and vasodilatory effects of epidermal growth factor: the role of sensory afferent neurons.
Epidermal growth factor (EGF) has been shown to exert gastric hyperemic and gastroprotective effects via capsaicin-sensitive afferent neurons, including the release of calcitonin gene-related peptide (CGRP). We examined the protective and vasodilatory effects of EGF on the gastric mucosa and its interaction with sensory nerves, CGRP, and nitric oxide (NO) in anesthetized rats. Intragastric EGF (10 or 30 microg) significantly reduced gastric mucosal lesions induced by intragastric 60% ethanol (50.6% by 10 microg EGF and 70.0% by 30 microg EGF). The protective effect of EGF was significantly inhibited by pretreatment with capsaicin desensitization, human CGRP1 antagonist hCGRP-(8-37), or N(omega)-nitro-L-arginine methyl ester (L-NAME). Intravital microscopy showed that topically applied EGF (10-1,000 microg/ml) dilated the gastric mucosal arterioles dose dependently and that this vasodilatory effect was significantly inhibited by equivalent pretreatments. These findings suggest that EGF plays a protective role against ethanol-induced gastric mucosal injury, possibly by dilating the gastric mucosal arterioles via capsaicin-sensitive afferent neurons involving CGRP and NO mechanisms.
Matsumoto
Y
Y
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan. yoji@intmed2.med.kyushu-u.ac.jp
Kanamoto
K
K
Kawakubo
K
K
Aomi
H
H
Matsumoto
T
T
Ibayashi
S
S
Fujishima
M
M
D000344:Afferent Pathways / Q000187:drug effects / Q000473:pathology; D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002211:Capsaicin / Q000633:toxicity; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D000431:Ethanol / Q000633:toxicity; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000294:innervation / Q000473:pathology; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D000431:Ethanol; D004815:Epidermal Growth Factor; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D019331:NG-Nitroarginine Methyl Ester