ISSN:
1432-1912
Keywords:
Substance P
;
Neurokinin A
;
Tachykinin receptors
;
Enteric reflexes
;
Rat duodenum
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract The study aimed to establish the possible role of tachykinins as mediators of atropine-resistant reflex contractions evoked by balloon distension in the proximal duodenum of urethane-anesthetized, guanethidine (34 μmol/kg s.c.)-pretreated rats. Distension of the balloon with a small amount (0.2–0.3 ml) of saline induced the appearance of phasic rhythmic contractions (about 11 mmHg in amplitude) which were promptly suppressed by either atropine (3 μmol/kg i.v.) or hexamethonium (28 μmol/kg i.v.). Despite the continuous i.v. infusion of atropine (2 μmol/h), low-amplitude rhythmic phasic contractions recovered, which were promptly suppressed by hexamethonium, to indicate the involvement of an atropine-resistant excitatory reflex. The amplitude of these atropine-resistant contractions was increased to about 4–5 mmHg by further distension of the balloon (0.4–0.6 ml) : under these conditions, the atropine-resistant contractions undergo a progressive fading. The fading was prevented by i.v. administration of the nitric oxide (NO) synthase inhibitor, L-nitroarginine methyl ester (L-NAME, 55 μmol/h), to provide a suitable baseline (amplitude of contractions was 7–8 mmHg) for studying the effect of tachykinin receptor antagonists. I.v. administration of the selective tachykinin NK2 receptor antagonists, MEN 10,627 (10–100 nmol/kg) and SR 48968 (100–300 nmol/kg) or of the selective NK1 antagonist SR 140333 (100 nmol/kg), at doses which do not affect the duodenal contractions induced by acetylcholine (5.5 µmol/kg i.v.), produced a prompt and long lasting suppression of the atropine-resistant reflex duodenal contractions produced by balloon distension in urethane-anesthetized rats, whilst SR 48965 (300 nmol/kg), the enantiomer of SR 48968 devoid of NK2 receptor blocking activity, was without effect. I.v. administration of the selective NKi receptor agonists [Sar9] substance P sulfone and septide or of the NK2 receptor selective agonist, βAla8] neurokinin A(4–10) produced dose-dependent contractions of the duodenum. SR 140333 (100 nmol/kg i.v.) selectively antagonized the duodenal contractions produced by [Sar9] substance P sulfone and septide without affecting those produced by [βAla8] neurokinin A(4–10). On the other hand, MEN 10,627 (30–100 nmol/kg i.v.) and SR 48968 (100–300 nmol/kg i.v.) but not SR 48965 (300 nmol/kg i.v.) antagonized, at a comparable extent, duodenal contractions induced by both the selective NK2 and NK1 receptor agonists. We conclude that endogenous tachykinins are involved in mediating atropine-resistant reflex contractions evoked by distension of the rat duodenum in vivo: both NK1 and NK2 receptors are activated by endogenous ligands to produce NANC contractions of rat duodenum in vivo. However, the contractile response to i.v. administered NK1 receptor agonists, [Sar9] substance P sulfone and septide, may involve the release of mediators producing smooth muscle contraction via NK2 receptors.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00171064
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