Angiotensin II-induced activation of central AT1 receptors exerts endocannabinoid-mediated gastroprotective effect in rats

K. Gyires, A. Rónai, Z. Zádori, Viktória E. Tóth, J. Németh, Mária Szekeres, L. Hunyady

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Abstract

The aim of the present study was to analyze whether angiotensin II via the endocannabinoid system can induce gastric mucosal protection, since transactivation of cannabinoid CB1 receptors by angiotensin AT1 receptor in CHO cells was described. Experimental ulcer was induced by acidified ethanol given orally in male Wistar rats, CB1(+/+) wild type and CB1(-/-) knockout mice. The compounds were administered intracerebroventricularly. It was found, that 1. Angiotensin II inhibited the ethanol-induced gastric lesions (11.9-191pmol); the effect of angiotensin II (191pmol) was inhibited by the CB1 receptor inverse agonist AM 251 (1.8nmol) and the inhibitor of diacylglycerol lipase (DAGL), tetrahydrolipstatin (0.2nmol). 2. Angiotensin II exerted gastroprotection in wild type, but not in CB1(-/-) mice. 3. The gastroprotective effect of angiotensin II (191pmol) was reduced by atropine (1mg/kg i.v.) and bilateral cervical vagotomy. In conclusion, stimulation of central angiotensin AT1 receptors via activation of cannabinoid CB1 receptors induces gastroprotection in a DAGL-dependent and vagus-mediated mechanism.

Original languageEnglish
Pages (from-to)971-978
Number of pages8
JournalMolecular and Cellular Endocrinology
Volume382
Issue number2
DOIs
Publication statusPublished - Feb 15 2014

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Endocannabinoids
Angiotensin II
Rats
Cannabinoid Receptor CB1
Chemical activation
Angiotensin Type 1 Receptor
Lipoprotein Lipase
Stomach
Ethanol
CHO Cells
Vagotomy
Atropine
Knockout Mice
Transcriptional Activation
Ulcer
Wistar Rats

Keywords

  • Angiotensin II
  • CB KO mice
  • Endocannabinoids
  • Gastroprotection
  • Rat

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Biochemistry

Cite this

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title = "Angiotensin II-induced activation of central AT1 receptors exerts endocannabinoid-mediated gastroprotective effect in rats",
abstract = "The aim of the present study was to analyze whether angiotensin II via the endocannabinoid system can induce gastric mucosal protection, since transactivation of cannabinoid CB1 receptors by angiotensin AT1 receptor in CHO cells was described. Experimental ulcer was induced by acidified ethanol given orally in male Wistar rats, CB1(+/+) wild type and CB1(-/-) knockout mice. The compounds were administered intracerebroventricularly. It was found, that 1. Angiotensin II inhibited the ethanol-induced gastric lesions (11.9-191pmol); the effect of angiotensin II (191pmol) was inhibited by the CB1 receptor inverse agonist AM 251 (1.8nmol) and the inhibitor of diacylglycerol lipase (DAGL), tetrahydrolipstatin (0.2nmol). 2. Angiotensin II exerted gastroprotection in wild type, but not in CB1(-/-) mice. 3. The gastroprotective effect of angiotensin II (191pmol) was reduced by atropine (1mg/kg i.v.) and bilateral cervical vagotomy. In conclusion, stimulation of central angiotensin AT1 receptors via activation of cannabinoid CB1 receptors induces gastroprotection in a DAGL-dependent and vagus-mediated mechanism.",
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T1 - Angiotensin II-induced activation of central AT1 receptors exerts endocannabinoid-mediated gastroprotective effect in rats

AU - Gyires, K.

AU - Rónai, A.

AU - Zádori, Z.

AU - Tóth, Viktória E.

AU - Németh, J.

AU - Szekeres, Mária

AU - Hunyady, L.

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