Both α2B- and α2C-adrenoceptor subtypes are involved in the mediation of centrally induced gastroprotection in mice

Dual Alpha2C/5HT1A Receptor Agonist Allyphenyline Induces Gastroprotection and Inhibits Fundic and Colonic Contractility

“…We demonstrated that clonidine and rilmenidine, when given either peripherally (per os, subcutaneously) or centrally (i.c.v. ), inhibited potently the direct necrotizing action of acidified ethanol on gastric mucosa in both rats and mice [12][13][14][15][16][17]. Our results also showed that the site of action is presumably within the CNS [16,17], where the activation of α2B-and α2C-ARs initiates a chain of events resulting in vagally mediated release of mucosal protective factors, such as prostaglandins and nitric oxide [13,16].…”

“…More importantly, our results clearly showed that this protective effect is mediated by α2B-and α2C-ARs localized in the brain, most probably in the dorsal vagal complex, and α2A-ARs do not have any significant role in it [12,14,17]. Accordingly, we proposed that selective α2B/C-AR agonists may represent a novel group of gastroprotective agents, which are devoid of several side effects mediated by the α2A-AR subtype, such as hypotension, bradycardia or sedation [17].…”

“…More importantly, our results clearly showed that this protective effect is mediated by α2B-and α2C-ARs localized in the brain, most probably in the dorsal vagal complex, and α2A-ARs do not have any significant role in it [12,14,17]. Accordingly, we proposed that selective α2B/C-AR agonists may represent a novel group of gastroprotective agents, which are devoid of several side effects mediated by the α2A-AR subtype, such as hypotension, bradycardia or sedation [17]. However, although the site of gastroprotective action is likely to be central, it should be considered that α2B-ARs are located also postsynaptically on vessels [18,19] and appear to be involved in the vasoconstrictor response to α2-AR agonists [20] and in salt-induced hypertension [21].…”

“…), inhibited potently the direct necrotizing action of acidified ethanol on gastric mucosa in both rats and mice [12][13][14][15][16][17]. Our results also showed that the site of action is presumably within the CNS [16,17], where the activation of α2B-and α2C-ARs initiates a chain of events resulting in vagally mediated release of mucosal protective factors, such as prostaglandins and nitric oxide [13,16]. Because α2-AR agonists are widely used as antihypertensive drugs, as adjuncts to anesthetics and analgesics during the perioperative period, or as drugs to treat opiate withdrawal or attentiondeficit/hyperactivity disorder [50], a potential anti-ulcer effect is of high clinical relevance.…”

“…In the last two decades our research group demonstrated that α2-AR agonists induce a potent defensive effect in the stomach and reduce the extent of mucosal injury in both aciddependent (indomethacin) and independent (ethanol) ulcer models [12][13][14][15][16][17]. More importantly, our results clearly showed that this protective effect is mediated by α2B-and α2C-ARs localized in the brain, most probably in the dorsal vagal complex, and α2A-ARs do not have any significant role in it [12,14,17].…”