Disturbance of the prejunctional modulation of cholinergic neurotransmission during chronic granulomatous inflammation of the mouse ileum

Abstract

1 The e ect of chronic granulomatous in¯ammation of the intestine was studied on the prejunctional modulation of cholinergic nerve activity in the mouse ileum. 2 Contractions to carbachol (0.01 ± 0.3 mM) and to electrical ®eld stimulation (EFS, 0.25 ± 8 Hz) of enteric neurons were higher in in¯amed ileum as compared to control ileum. However, when the neurally-mediated contractions to EFS were expressed as percentage of the direct smooth muscle contraction to carbachol, the responses to EFS were similar in control and in¯amed ileum. 3 Atropine (1 mM) abolished all contractions to EFS and carbachol in control and in¯amed ileum. DMPP (3 ± 30 mM), a nicotinic receptor agonist, induced concentration-dependent contractions that were more pronounced in in¯amed ileum as compared to control ileum. Hexamethonium (100 mM), a nicotinic receptor blocker, signi®cantly inhibited the contractions to EFS in in¯amed ileum but not in control ileum. 4 In control ileum, histamine (10 ± 100 mM) and the histamine H 1 receptor agonist HTMT (3 ± 10 mM) inhibited the contractions to EFS concentration-dependently without a ecting the contractions to carbachol. The inhibitory e ect of histamine and HTMT was prevented by the histamine H 1 antagonist mepyramine (5 ± 10 mM) but not by the H 2 -and H 3 -receptor antagonists cimetidine and thioperamide (both 10 mM). In chronically in¯amed ileum however, histamine (10 ± 100 mM) and HTMT (3 ± 10 mM) failed to inhibit the contractions to EFS. The histamine H 2 and H 3 receptor agonists dimaprit and R(7)-a-methylhistamine did not a ect the contractions to EFS in control and in¯amed ileum. 5 The a 2 -receptor agonist UK 14.304 (0.01 ± 0.1 mM) inhibited the contractions to EFS in control and in¯amed ileum without a ecting the contractions to carbachol. The e ect of UK 14.304 was reversed by the a 2 -receptor antagonist yohimbine (1 mM). The inhibitory e ect of UK 14.304 on contractions to EFS was of similar potency in control and in¯amed ileum. 6 Our results suggest that the prejunctional modulation of cholinergic nerve activity by nicotinic and histaminic H 1 receptors is disturbed during chronic intestinal in¯ammation whereas the modulation by a 2 -receptors is preserved. Such a disturbance of cholinergic nerve activity may contribute to the motility disturbances that are often observed during chronic intestinal diseases in humans.

The endogenous cannabinoid system protects against colonic inflammation

“…Contractility of smooth muscle to cholinergic or tachykinergic stimuli is increased in the early stages and decreased in the later stages of inflammation (38,39), and contractility following electrical neuronal stimulation in the inflamed gut is increased (40). The electrophysiological changes in the distal colon, as used in this study, show increased smooth muscular excitability, leading to the occurrence of spontaneous spiking activity.…”

Adenosine 2B receptors (A2BAR) on enteric neurons regulate murine distal colonic motility

“…The A 2B AR has been identified in various biological functions, including vasodilation, inhibition of endothelial smooth muscle growth, allergy, and inflammation reactions (13, 17, 24‐28). In the present study, we investigated the functional importance of the enteric neuronal A 2B AR in modulating distal colonic motility.…”

Modulation of airway inflammation and resistance in mice by a nicotinic receptor agonist

“…Some studies showed smooth muscle relaxation [28], others showed contraction [29]. One study showed that DMPP reduces the bronchomotor tone in cats [19].…”