Galanin modulates vagally induced contractions in the mouse oesophagus

Abstract

Nitrergic myenteric neurons co-innervating motor endplates were previously shown to inhibit vagally induced contractions of striated muscle in the rodent oesophagus. Immunohistochemical demonstration of putative co-transmitters, e.g. galanin, in enteric neurons prompted us to study a possible role of galanin in modulating vagally mediated contractions in an in vitro vagus nerve-oesophagus preparation of the mouse. Galanin (1-16) (1-100 nmol L(-1)), in the presence of the peptidase inhibitor, phenanthroline monohydrate, inhibited vagally induced contractions in a concentration-dependent manner (control: 100%; galanin 1 nmol L(-1): 95.6 +/- 1.6%; galanin 10 nmol L(-1): 57.3 +/- 6.5%; galanin 100 nmol L(-1): 31.2 +/- 8.1%, n = 5). The non-selective galanin receptor antagonist, galantide (100 nmol L(-1)), blocked the inhibitory effect of galanin (10 nmol L(-1)) while the selective non-galanin receptor 1 and galanin receptor 3 antagonists, M871 (1 micromol L(-1)) and SNAP37889 (100 nmol L(-1)), respectively, and the nitric oxide synthase inhibitor, NG-nitro-l-arginine methyl ester (L-NAME) (200 micromol L(-1)), failed to affect this galanin-induced response. Simultaneous application of galantide (100 nmol L(-1)) and L-NAME (200 micromol L(-1)) significantly reduced the inhibitory effect of capsaicin (30 mumol L(-1)) on vagally induced contractions when compared with its effect in the presence of L-NAME alone or in combination with the selective galanin receptor 2 or 3 antagonists. An inhibitory effect of piperine on vagally induced contractions was reduced neither by galantide nor by L-NAME. Immunohistochemistry revealed galanin immunoreactive myenteric neurons and nerve fibres intermingling with cholinergic vagal terminals at motor endplates. These data suggest that galanin from co-innervating enteric neurons co-operates with nitric oxide in modulating vagally induced contractions in the mouse oesophagus.

Involvement of TRPV2 Activation in Intestinal Movement through Nitric Oxide Production in Mice

“…Spontaneous intestinal contractions of circular muscle were recorded as described previously (Penuelas et al, 2007;Boudaka et al, 2009). Briefly, 8-to 12-week-old male WT mice were killed by cervical dislocation.…”

Contractile Properties of Esophageal Striated Muscle: Comparison with Cardiac and Skeletal Muscles in Rats

“…Morphological studies have shown that esophageal striated muscle receives dual innervation from both vagal motor fibers originating in the brainstem and varicose intrinsic nerve fibers originating in the myenteric plexus, which is called “enteric coinnervation” of esophageal motor endplates [3, 17]. We have also provided evidence that a local neural reflex pathway in the esophagus, consisting of primary afferent neurons and myenteric neurons, can modulate motility of the striated muscle portion of the esophagus [18–21]. Thus, both extrinsic and intrinsic neural regulations would be important in coordinating the peristaltic motility of the esophagus.…”

Peripheral cardiac sympathetic hyperactivity in cardiovascular disease: role of neuropeptides

“…The release of galanin can also be detected in vitro but at lower levels than that observed for NPY (39). Evidence for galinin release as a cotransmitter under conditions of high sympathetic stimulation has also been reported within the liver and the gut (7,51) Antagonists of the Y 2 receptor and GALR1 can reverse the inhibition of vagal bradycardia inhibition postsympathetic stimulation in vitro (39) and in vivo (104) as can genetic knockout of these receptors in vivo (88,105,106). Immunohistochemical labeling has localized the NPY Y 2 receptor (41) as well as the galanin GalR1 receptor (39) to vagal neurons in the right atria and around the sinoatrial node providing the anatomical basis for the sympathovagal cross-talk model.…”