Brain-derived neurotrophic factor enhances cholinergic contraction of longitudinal muscle of rabbit intestine via activation of phospholipase C

Qudah, Mohammad Al; Anderson, Charles D.; Mahavadi, Sunila; Bradley, Zachary L.; Akbarali, Hamid I.; Murthy, Karnam S.; Grider, John R.

doi:10.1152/ajpgi.00203.2013

Cited by 40 publications

(57 citation statements)

References 58 publications

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“…Preliminary studies (data not shown) indicated that BDNF synthesis and secretion are not affected by acetylcholine. This is consistent with the lack of effect of Trk B antagonists and antiserum alone on the BDNF‐induced augmentation of cholinergic contractions . Substance P increased the expression of BDNF to approximately the same degree as did PACAP.…”

Section: Discussionsupporting

confidence: 82%

Stimulation of synthesis and release of brain‐derived neurotropic factor from intestinal smooth muscle cells by substance P and pituitary adenylate cyclase‐activating peptide

Qudah

Alkahtani

Akbarali

et al. 2015

Neurogastroenterology Motil

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Background Brain-derived neurotrophic factor (BDNF) is a neurotrophin present in the intestine where it participates in survival and growth of enteric neurons, augmentation of enteric circuits, and stimulation of intestinal peristalsis and propulsion. Previous studies largely focused on the role of neural and mucosal BDNF. The expression and release of BDNF from intestinal smooth muscle and the interaction with enteric neuropeptides has not been studied in gut. Methods The expression and secretion of BDNF from smooth muscle cultured from rabbit longitudinal intestinal muscle in response to substance P and pituitary adenylate cyclase activating peptide (PACAP) was measured by western blot and ELISA. BDNF mRNA was measured by rt-PCR. Key Results The expression of BNDF protein and mRNA was greater in smooth muscle cells from the longitudinal muscle than from circular muscle layer. PACAP and substance P increased the expression of BDNF protein and mRNA in cultured longitudinal smooth muscle cells. PACAP and substance P also stimulated the secretion of BDNF from cultured longitudinal smooth muscle cells. Chelation of intracellular calcium with BAPTA prevented substance P-induced increase in BDNF mRNA and protein expression as well as substance P-induced secretion of BDNF. Conclusions & Inferences Neuropeptides known to be present in enteric neurons innervating the longitudinal layer increase the expression of BDNF mRNA and protein in smooth muscle cells and stimulate the release of BDNF. Considering the ability of BDNF to enhance smooth muscle contraction, this autocrine loop may partially explain the characteristic hypercontractility of longitudinal muscle in inflammatory bowel disease.

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Section: Discussionsupporting

confidence: 82%

Stimulation of synthesis and release of brain‐derived neurotropic factor from intestinal smooth muscle cells by substance P and pituitary adenylate cyclase‐activating peptide

Qudah

Alkahtani

Akbarali

et al. 2015

Neurogastroenterology Motil

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“…This compound selectively binds and activates the BDNF receptor, TrkB, and initiates its intracellular signaling pathways in vitro and in vivo (40, 66–68). Previous studies showed that LM22A-4 activates ERK signaling via TrkB (67, 69, 70) and that BDNF reduced alcohol drinking via the activation of ERK signaling (19).…”

Section: Discussionmentioning

confidence: 99%

The BDNF Valine 68 to Methionine Polymorphism Increases Compulsive Alcohol Drinking in Mice That Is Reversed by Tropomyosin Receptor Kinase B Activation

Warnault

Darcq

Morisot

et al. 2016

Biological Psychiatry

123

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Background The Val66 to Met polymorphism within the brain-derived neurotrophic factor (BDNF) sequence reduces activity-dependent BDNF release, and is associated with psychiatric disorders in humans. Alcoholism is one of the most prevalent psychiatric diseases. Here, we tested the hypothesis that this polymorphism increases the severity of alcohol abuse disorders. Methods We generated transgenic mice carrying the mouse homolog of the human Met66BDNF allele (Met68BDNF), and used alcohol-drinking paradigms in combination with viral-mediated gene delivery and pharmacology. Results We found that Met68BDNF mice consumed excessive amounts of alcohol and continued to drink despite negative consequences, a hallmark of addiction. Importantly, compulsive alcohol intake was reversed by overexpression of the wild-type Val68BDNF allele in the ventromedial prefrontal cortex of the Met68BDNF mice, or by systemic administration of the TrkB agonist, LM22A-4. Conclusions Our findings suggest that carrying the Met66BDNF allele increases the risk of developing uncontrolled and excessive alcohol drinking that can be reversed by directly activating the BDNF receptor, TrkB. Importantly, this work identifies a potential therapeutic strategy for the treatment of compulsive alcohol drinking in humans carrying the Met66BDNF allele.

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“…Bladder compliance was determined using the formula, (V N − V M )/(P N − P M ), where V represents bladder capacity, P represents bladder pressure, M represents initiation of bladder filling and N represents initiation of voiding. 20 …”

Section: Methodsmentioning

confidence: 99%

“…In addition, bladder wall thickening causes poor detrusor smooth muscle compliance and affects smooth muscle contractility. 20 Thus, the role of NMDAR in regulating bladder function during cystitis was also investigated.…”

mentioning

confidence: 99%

Inhibition of NMDAR Reduces Bladder Hypertrophy and Improves Bladder Function in Cyclophosphamide Induced Cystitis

et al. 2015

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Purpose We examined the role of NMDAR in the regulation of bladder hypertrophy and function in a rat model of cyclophosphamide induced cystitis. Materials and Methods Cystitis was induced by intraperitoneal injection of cyclophosphamide (150 mg/kg body weight). NMDAR phosphorylation (activity) and signal transduction pathways were examined by direct measurement and by specific inhibitors in vivo. Bladder hypertrophy was measured by bladder weight/body weight and type I collagen expression. Bladder function was examined by metabolic recording, conscious cystometry and detrusor muscle strip contractility in response to carbachol. Results NMDAR activity measured by the phosphorylation level of the NMDAR1 (NR1) subunit was expressed in the spinal cord but not in the bladder at 48 hours of cystitis. NMDAR inhibition with dizocilpine (MK-801) reduced the cystitis induced increment of bladder weight and type I collagen up-regulation in the bladder. NMDAR regulated type I collagen up-regulation was mediated by the PI3K/Akt pathway. NMDAR inhibition also attenuated cystitis induced urinary frequency measured by metabolic cage and cystometry. Cystitis decreased the responsiveness of detrusor muscle strips to carbachol, which was reversed by MK-801 in vivo. Unlike MK-801 the NMDAR antagonist D-AP5, which could not block central NMDAR activity, had no effect on bladder hypertrophy, type I collagen up-regulation or Akt activation caused by cystitis in the bladder. Conclusions Findings suggest that NMDAR activity has a role in cystitis induced bladder hypertrophy and overactivity. NMDAR mediated Akt activation may underlie the mechanism of bladder dysfunction.

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Brain-derived neurotrophic factor enhances cholinergic contraction of longitudinal muscle of rabbit intestine via activation of phospholipase C

Cited by 40 publications

References 58 publications

Stimulation of synthesis and release of brain‐derived neurotropic factor from intestinal smooth muscle cells by substance P and pituitary adenylate cyclase‐activating peptide

Stimulation of synthesis and release of brain‐derived neurotropic factor from intestinal smooth muscle cells by substance P and pituitary adenylate cyclase‐activating peptide

The BDNF Valine 68 to Methionine Polymorphism Increases Compulsive Alcohol Drinking in Mice That Is Reversed by Tropomyosin Receptor Kinase B Activation

Inhibition of NMDAR Reduces Bladder Hypertrophy and Improves Bladder Function in Cyclophosphamide Induced Cystitis

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