Gastroprotective actions of bombesin, L-DOPA, and mild irritants: roles of prostaglandins and sensory neurons.
BACKGROUND
Bombesin and dopamine prevent gastric injury by an unknown mechanism. Sensory neurons and endogenous prostaglandins play an important role in gastric mucosal defense. This study was designed to assess the role of these two local defense mechanisms in bombesin and dopamine-induced gastroprotection, as well as mild irritant-induced adaptive cytoprotection.


METHODS
Conscious, fasted rats were given either capsaicin (125 mg/kg subcutaneously) to ablate sensory neurons or indomethacin (5 mg/kg intraperitoneally) to inhibit prostaglandin synthesis, 2 weeks and 30 minutes, respectively, before administration of bombesin (100 micrograms/kg subcutaneously), the dopamine precursor L-DOPA (25 mg/kg intraperitoneally), or the mild irritant 25% ethanol (1 mL orogastric). A 1-mL orogastric bolus of acidified ethanol (150 mmol/L HCl/50% ethanol) was given 30 minutes after pretreatment with these peptides and 15 minutes after administration of the mild irritant. Rats were killed 5 minutes later and the total area of macroscopic gastric injury quantified.


RESULTS
Ablation of sensory neurons with capsaicin negated the protective actions of bombesin but failed to reverse gastroprotection by L-DOPA or 25% ethanol. Cyclooxygenase inhibition with indomethacin partially reversed bombesin and mild irritant-induced gastroprotection but did not diminish the protective actions of L-DOPA.


CONCLUSIONS
Bombesin requires intact sensory neurons to exert its protective actions through a mechanism mediated, at least in part, by endogenous prostaglandins. Adaptive cytoprotection by the mild irritant 25% ethanol requires the presence of endogenous prostaglandins but not sensory neurons. L-DOPA-induced gastroprotection is independent of both local defense mechanisms.
Mercer
D W
DW
Department of Surgery, University of Texas-Houston Medical School 77030, USA.
Cross
J M
JM
Castaneda
A A
AA
Gunter
J A
JA
D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D001839:Bombesin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007509:Irritants / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007980:Levodopa / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000502:physiology; D013270:Stomach / Q000187:drug effects*
D016861:Cyclooxygenase Inhibitors; D015259:Dopamine Agents; D007509:Irritants; D011453:Prostaglandins; D011949:Receptors, Cholecystokinin; D000431:Ethanol; D007980:Levodopa; D001839:Bombesin; D002211:Capsaicin; D007213:Indomethacin