Effects of DJ-7141, a new peripherally acting alpha-2 adrenoceptor agonist, on blood pressure and gastric acid output in rats: evidence for the heterogeneity of alpha-2 adrenoceptors in different organs.
Effects of intravenously administered clonidine and DJ-7141 on blood pressure and gastric acid output were studied in anesthetized rats. Both drugs caused a dose-dependent increase in blood pressure. Clonidine-induced increases in the blood pressure were attenuated by yohimbine and prazosin. DJ-7141-induced increases in blood pressure were also attenuated by yohimbine, but were little affected even by a large dose of prazosin. Splanchnic nerve stimulation-induced increases in blood pressure were attenuated by clonidine and DJ-7141. The inhibitory effects of DJ-7141 exceeded those of clonidine. On the other hand, these agonists had no effect on exogenously applied norepinephrine-induced increases in blood pressure. Vagally stimulated gastric acid output was inhibited by small doses of clonidine and large doses of DJ-7141. Clonidine-induced inhibition of acid output was abolished by yohimbine (5 mg/kg), but not by prazosin (5 mg/kg). In contrast, the DJ-7141-induced inhibition of acid output was not affected by yohimbine (5 mg/kg), but was attenuated by a small dose of prazosin (0.1 mg/kg). These results indicate that DJ-7141 had no effect on alpha-2 adrenoceptors in gastric parasympathetic nerves. Furthermore, the alpha-2 adrenoceptors on parasympathetic nerves in the gastric wall are probably pharmacologically different from those on sympathetic nerves and blood vessels in rats.
D000316:Adrenergic alpha-Agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003000:Clonidine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D007093:Imidazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013153:Splanchnic Nerves / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; C049769:DJ 7141; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin