Functional and in situ hybridization evidence that preganglionic sympathetic vasoconstrictor neurons express ghrelin receptors

Ferens, Dorota; Yin, Lei; Bron, Romke; Hunne, Billie; Ohashi-Doi, Katsuyo; Kitchener, PD; Sanger, Gareth J.; Witherington, Jason; Shimizu, Yasutake; Furness, John B.

doi:10.1016/j.neuroscience.2010.01.001

Cited by 43 publications

(74 citation statements)

References 28 publications

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“…This and other ghrelin receptor agonists that cross the blood-brain barrier, and ghrelin applied directly to the spinal cord, stimulate autonomic preganglionic neurons that express the ghrelin receptor. 3,5,9 SCI at cervical or thoracic levels disrupts descending inputs that control the lumbosacral defecation centers. .…”

Section: Discussionmentioning

confidence: 99%

“…Unlike the dysreflexic blood pressure increases that occur when the colon is distended in spinal cord-injured rats, 17 the events in the colon and the blood pressure changes that are observed in response to ghrelin agonists in rats without SCI are independent. 5,9 When they are applied at sites rostral to the defecation centers in normal animals (and rostral to the site of SCI used in the current experiments), ghrelin receptor agonists only elicit blood pressure responses (maximal blood pressure effects are from T9 to T12) and only small blood pressure increases are elicited from the levels of the defecation centers at L1 to L3. 9 Moreover, the effects on the colon can be blocked pharmacologically without affecting the blood pressure increases that occur when ghrelin receptors are activated.…”

Section: Discussionmentioning

confidence: 99%

“…5,9 When they are applied at sites rostral to the defecation centers in normal animals (and rostral to the site of SCI used in the current experiments), ghrelin receptor agonists only elicit blood pressure responses (maximal blood pressure effects are from T9 to T12) and only small blood pressure increases are elicited from the levels of the defecation centers at L1 to L3. 9 Moreover, the effects on the colon can be blocked pharmacologically without affecting the blood pressure increases that occur when ghrelin receptors are activated. 5 It remains possible that if the SCI had been above T5, a level that in rats severs the bulbospinal pathways controlling the splanchnic circulation, hyper-reflexic blood pressure responses would have been elicited.…”

Section: Discussionmentioning

confidence: 99%

“…We have been unable to locate any published data that indicate that centrally penetrant ghrelin receptor agonists increase blood pressure in human. In fact, it appears that the peripheral vasodilator effects of ghrelin agonists, which have been well-documented in animal studies, 9 dominate in humans. 18 Ghrelin itself, which does not cross into the spinal cord, also lowers blood pressure in human.…”

Section: Discussionmentioning

confidence: 99%

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Stimulation of defecation in spinal cord-injured rats by a centrally acting ghrelin receptor agonist

et al. 2011

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Methods: Rats were subjected to spinal cord contusion injury or were sham-operated. At 6 weeks after surgery, effects of capromorelin on blood pressure, heart rate and propulsive contractions of the colorectum were investigated. Results: Capromorelin caused robust propulsive activity in the colorectum soon after its application. The compound was similarly effective in naïve, sham-operated and spinal cord-injured rats. Blood pressure increases caused by capromorelin were not exaggerated after SCI, and there was no evidence of phasic blood pressure increases when the colon was contracted by the compound. Conclusion: Capromorelin is a therapeutic compound that could potentially be used to relieve constipation by triggering defecation in spinal cord-injured patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Stimulation of defecation in spinal cord-injured rats by a centrally acting ghrelin receptor agonist

et al. 2011

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“…Ghrelin receptor expression in humans has been identified in various organs, including the kidney (21,(40)(41)(42)(43), where it is predominantly located on tubular rather than glomerular cells (44). A previous report showed that ghrelin increased serum IGF-1 concentrations and that IGF-1 exerted renal protection.…”

Section: Discussionmentioning

confidence: 99%

Plasma ghrelin levels as a predictor of adverse renal events due to cisplatin-based chemotherapy in patients with esophageal cancer

Yanagimoto

Takiguchi

Miyazaki

et al. 2016

Japanese Journal of Clinical Oncology

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Objective: Although combination chemotherapy with docetaxel, cisplatin and 5-fluorouracil demonstrates high response rates in esophageal squamous cell carcinoma, patients treated with docetaxel, cisplatin and 5-fluorouracil frequently experience acute kidney injury. Ghrelin has shown renal protective effects in an experimental acute kidney injury model by reducing tubular apoptosis. In this prospective observational study, we evaluated the association between plasma ghrelin concentrations and docetaxel, cisplatin and 5-fluorouracil-related acute kidney injury. Methods: Forty consecutive patients with esophageal squamous cell carcinoma who received docetaxel, cisplatin and 5-fluorouracil from October 2013 to July 2014 were enrolled in this study. Serum creatinine and urinary α-1 microglobulin, a marker of renal tubular damage, were measured six times during chemotherapy. Results: The increases of creatinine level which is defined in Common Terminology Criteria for Adverse Event were observed less frequently in patients with acyl ghrelin concentrations of ≥9.6 fmol/ml (HAG group) than in those with concentrations <9.6 fmol/ml on Day 2 (LAG group) (P = 0.024). Serum creatinine was significantly lower in the HAG group than in the LAG group (Day 8: 0.79 ± 0.16 vs. 0.97 ± 0.26, P = 0.024; Day 11: 0.85 ± 0.19 vs. 1.08 ± 0.34 mg/dl, P = 0.049). Urinary α-1 microglobulin levels were significantly lower in the HAG group than in the LAG group (Day 4: 2.48 ± 1.83 vs. 3.33 ± 1.41, P = 0.011; Day 8: 4.67 ± 5.50 vs. 5.09 ± 2.54, P = 0.011; Day 11: 11.55 ± 13.78 vs. 16.43 ± 17.84 mg/l, P = 0.020). Conclusions: Plasma acyl ghrelin concentrations on Day 2 of chemotherapy may be a potential predictor of docetaxel, cisplatin and 5-fluorouracil-induced acute kidney injury.

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Expression of the ghrelin receptor gene in neurons of the medulla oblongata of the rat

Bron

Yin

Russo

et al. 2013

J of Comparative Neurology

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There is ambiguity concerning the distribution of neurons that express the ghrelin receptor (GHSR) in the medulla oblongata. In the current study we used a sensitive nonradioactive method to investigate GHSR mRNA distribution by in situ hybridization. Strong expression of the GHSR gene was confirmed in neurons of the facial nucleus (FacN, 7), the dorsal vagal complex (DVC), and the semicompact (but not compact) nucleus ambiguus (AmbSC and AmbC). In addition, expression of GHSR was found in other regions, where it had not been described before. GHSR-positive neurons were observed in the gustatory rostral nucleus tractus solitarius and in areas involved in vestibulo-ocular processing (such as the medial vestibular nucleus and the nucleus abducens). GHSR expression was also noted in ventral areas associated with cardiorespiratory control, including the gigantocellular reticular nucleus, the lateral paragigantocellular nucleus, the rostral and caudal ventrolateral medulla, the (pre)-Bötzinger complex, and the rostral and caudal ventrolateral respiratory group. However, GHSR-positive neurons in ventrolateral areas did not express markers for cardiovascular presympathetic vasomotor neurons, respiratory propriobulbar rhythmogenic neurons, or sensory interneurons. GHSR-positive cells were intermingled with catecholamine neurons in the dorsal vagal complex but these populations did not overlap. Thus, the ghrelin receptor occurs in the medulla oblongata in 1) second-order sensory neurons processing gustatory, vestibulo-ocular, and visceral sensation; 2) cholinergic somatomotor neurons of the FacN and autonomic preganglionic neurons of the DMNX and AmbSC; 3) cardiovascular neurons in the DVC, Gi, and LPGi; 4) neurons of as yet unknown function in the ventrolateral medulla.

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Functional and in situ hybridization evidence that preganglionic sympathetic vasoconstrictor neurons express ghrelin receptors

Cited by 43 publications

References 28 publications

Stimulation of defecation in spinal cord-injured rats by a centrally acting ghrelin receptor agonist

Stimulation of defecation in spinal cord-injured rats by a centrally acting ghrelin receptor agonist

Plasma ghrelin levels as a predictor of adverse renal events due to cisplatin-based chemotherapy in patients with esophageal cancer

Expression of the ghrelin receptor gene in neurons of the medulla oblongata of the rat

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