Relaxation of canine gallbladder to nerve stimulation involves adrenergic and non‐adrenergic non‐cholinergic mechanisms

Abstract

Electrical field stimulation (EFS) of dog gallbladder strips induced a frequency-dependent contractile response followed by an off-relaxation that was turned into a pure inhibitory response after atropine pretreatment. Guanethidine reduced the atropine-induced relaxing responses, so an adrenergic mechanism can partially account for the nerve-mediated gallbladder relaxation. However, guanethidine pretreatment also revealed a nonadrenergic noncholinergic (NANC) relaxation induced by EFS, which was frequency independent. NANC relaxations were reduced by L-arginine methyl ester (L-NAME, 100 micromol L-1), a nitric oxide synthase inhibitor (D-p-Cl-Phe6, Leul7; 10 micromol L-1), a vasoactive intestinal peptide (VIP) receptor antagonist, and an inhibitor of haem oxygenase, (copper protoporphyrin IX; CuPP-IX; 10 micromol L-1), suggesting that nitric oxide (NO), VIP and carbon monoxide (CO), respectively, are released in response to EFS. Immunoreactivities for haem oxygenase-2 (HO-2) and VIP, and histochemical staining for NADPH diaphorase were observed in nerve cell bodies and fibres, demonstrating the presence of CO, VIP and NO as putative NANC neurotransmitters in dog gallbladder. These data support the hypothesis that NO, VIP and CO contribute to NANC relaxation of the canine gallbladder.

Characterization of the intrinsic and extrinsic innervation of the gall bladder epithelium in the Australian Brush‐tailed possum (Trichosurus vulpecula)

“…In the present study, we demonstrated the presence of NOS within neurones of the ganglionated subepithelial plexus which projected to the nonganglionated subepithelial plexus of the gall bladder. This defines for the first time, the source of the NO‐containing nerves of the nonganglionated subepithelial plexus, shown in previous studies, in several species 5,7–9 . This neuroanatomical data suggests a physiological role for NO in modulating gall bladder epithelial function, as has been defined within the gastrointestinal tract 45 .…”

“…The neurochemical content, including nitric oxide synthase (NOS) and vasoactive intestinal polypeptide (VIP) have been described in gall bladder neurones in several species. 3,[5][6][7][8][9] These intrinsic neurones of the gall bladder regulate its functions, 7,9,10 and we recently demonstrated that gall bladder motility is regulated by neurones of the muscular and serosal plexuses. 3 Notably, the origin of the nerve fibres within the nonganglionated subepithelial plexus, which are probably regulators of gall bladder epithelial function, require characterization.…”

Effects of NO/L-Arginine Pathway on Gallbladder Contractility in Bile Duct Ligated Guinea Pigs

“…NANC neurotransmission in the guinea pig gallbladder was described by Mourelle et al [6]. NO is the main NANC neurotransmitter involved in this system [17,18]. EF evokes a gallbladder smooth muscle response by the release of different inhibitory and excitatory neurotransmitters.…”

Effects of Melatonin on Gallbladder Neuromuscular Function in Acute Cholecystitis

“…Nonadrenergic noncholinergic neurotransmission in guinea pig gallbladder was described more than a decade ago (Mourelle et al, 1993), and NO is the main nonadrenergic noncholinergic neurotransmitter involved (McKirdy et al, 1994b;Alcón et al, 2001). Inflammation evokes a functional impairment in gallbladder nitrergic innervation as demonstrated by the lack of effects of L-NAME in cholecystitic strips compared with control tissue.…”