B. Beltran et al., Synthesis of nitric oxide in the dorsal motor nucleus of the vagus mediates the inhibition of gastric acid secretion by central bombesin, BR J PHARM, 127(7), 1999, pp. 1603-1610
1 Central administration of bombesin inhibits gastric acid production indep
endently of the centrally or peripherally-acting stimuli employed. This stu
dy evaluates the role and location of the cerebral nitric oxide (NO) implic
ated in the inhibitory effect of central bombesin on in vivo rat gastric ac
id secretion, as induced by distension with 15 cm H2O, insulin (0.75 u.i. k
g(-1) i.p.) TRH (1.2 mu g kg(-1), i.c.) or pentagastrin (100 mu g kg(-1), i
.p.).
2 The acid-inhibitory effect of i.c. bombesin (40 ng kg(-1)) was prevented
by prior administration of L-NAME (80 mu g kg(-1)) in the dorsal motor nucl
eus of the vagus (DMN). This dose of L-NAME when administered into the nucl
eus of the tractus solitarious (NTS) did not influence the effects of bombe
sin. Administration of L-arginine (400 mu g kg(-1)) into the DMN restored t
he acid-inhibitory effect of i.c. bombesin in animals treated with L-NAME.
3 Microinjection of bombesin (12 ng kg(-1)) into the paraventricular nucleu
s of the hypothalamus (PvN) inhibits acid secretion stimulated by pentagast
rin. This inhibitory effect was prevented by a previous injection of L-NAME
(80 mu g kg(-1)) into the DMN.
4 The release of NO in the DMN following i.c. administration of bombesin wa
s confirmed by in vivo electrochemical detection.
5 Administration by microdialysis in the DMN of the NO-donor SNAP (25 mM in
1.5 mu l min-L) into the DMN inhibits pentagastrin-stimulated gastric acid
secretion.
6 The present study suggests that nNOS-containing neurons in the DMN have a
n inhibitory role in the control of gastric acid responses.