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(-/-) knock out mice. The compounds were administered intracerebroventricularly. It was found, that 1./ Angiotensin II inhibited the ethanol-induced gastric lesions (11.9-191 pmol); the effect of angiotensin II (191 pmol) was inhibited by the CB1 receptor inverse agonist AM 251 (1.8 nmol) and the inhibitor of diacylglycerol lipase (DAGL), tetrahydrolipstatin (0.2 nmol). 2./ Angiotensin II exerted gastroprotection in wild type, but not in CB1(-/-) mice. 3./ The gastroprotective effect of angiotensin II (191 pmol) was reduced by atropine (1 mg/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.

Brain neuropeptides in gastric mucosal protection

“…Bell-shaped dose-reponse relationship was observed for example with RX 77368 (a stable TRH analog) [28], adrenomedullin [29], nociceptin and nocistatin [25], substance P [10] and angiotensin II [15]. In most cases the gastroprotective ranges varied between 10-fold and 100-fold, which is in agreement with the biphasic responses observed in other fields.…”

The Role of Capsaicin-Sensitive Afferent Nerves in Gastric Mucosal Protection Initiated Centrally or Peripherally under Experimental Conditions

“…μ-opioid receptors (in NTS and DMNV) [157], cannabinoid receptors (CB 1 -receptors in NTS and DMNV and CB 2 -receptors in NTS and brain stem neurons) [158,159] NK 1 -receptors in NTS and DMNV) [160,161], angiotensin AT 1 receptors in in the NTS, area postrema and DMNV [162,163] can influence gastric mucosal homeostasis. Our experimental results demonstrated that opioid peptides [4,133], anandamide, 2-arachidonoyl glycerol (2-AG) endocannabinoids, ligands of cannabinoid CB 1 and CB 2 receptors [137,142], as well as (SP) [136] given i.c.v. induced gastric mucosal protective effect against ethanol-induced lesions.…”

“…3.). Adapted from Gyires et al [137]. SP in pmolar dose range exerted mucosal protective action, the dose response curve proved to be bell shaped, similarly to 2-AG.…”

“…β-endorphin, deltorphin II, endomorphins [4,133] nociceptin, nocistatin [134], TLQP-21, a VGF-derived peptide [135], substance P [136] and angiotensin II [137] (see reviews: [4,127,138]). …”

A szteroidok elnevezése, felosztása és az emberi stresszfekélyek. Selye János 70 éve megjelent történelmi jelentőségű cikkei

“…A kísérleti adatok arra utalnak, hogy a vagusideg alapvető szerepet játszik a centrális hatás perifériára történő mediálásában, ugyanis vagusátmetszés, illetve az antikolinerg atropinelőkezelés megszüntette vagy csökkentette a centrálisan iniciált neuropeptidek többségének gyomorvédő hatását [68,69,70,71]. A vagus aktiválása a gyomormucosa területén számos, a mucosalis védelemben szerepet ját-szó endogén vegyület felszabadulását eredményezi.…”