Pre- and postsynaptic mechanisms in the clonidine- and oxymetazoline-induced inhibition of gastric motility in the rat.
The inhibitory effect of clonidine (non-selective alpha2-adrenoceptor agonist) and oxymetazoline (alpha2A-adrenoceptor selective agonist) was compared on basal and stimulated gastric motor activity (gastric tone and contractions) using the balloon method in the rat. It was shown that oxymetazoline (0.2-1.7 micromol/kg, i.v.) decreased the basal motility, while clonidine (1.9-3.8 micromol/kg, i.v.) failed to affect it. When motility was stimulated centrally by insulin (5 IU/rat, i.v.), both clonidine (1.9-3.8 micromol/kg, i.v.) and oxymetazoline (0.1-3.4 micromol/kg, i.v.) inhibited the gastric motor activity. However, while the effect of clonidine was antagonized by the non-selective alpha2-adrenoceptor antagonist yohimbine (5 micromol/kg, i.v.) and the alpha2A-adrenoceptor selective antagonist BRL 44408 (3 micromol/kg, i.v.), the effect of oxymetazoline was only partially affected. Prazosin (alpha1- and alpha2B-adrenoceptor antagonist, 0.07-0.28 micromol/kg, i.v.) also failed to reverse the effect of oxymetazoline. Furthermore, when gastric motility was stimulated peripherally by activation of postsynaptic cholinergic muscarinic receptors by the combination of carbachol (0.14 micromol/kg, i.v.) and hexamethonium (37 micromol/kg, i.v.), clonidine (3.8 micromol/kg, i.v.) failed to affect the increased motor activity, however, oxymetazoline (0.8-3.4 micromol/kg, i.v.) exerted a pronounced inhibition. These results suggest that different mechanisms may be involved in the inhibitory effect of clonidine and oxymetazoline; while clonidine reduces the gastric motility by activation of presynaptic alpha2-adrenoceptors, postsynaptic component in the effect of oxymetazoline has also been raised.
Zádori
Zoltán S
ZS
Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4, 1089 Budapest, Hungary. zadzol@net.sote.hu
Shujaa
Nashwan
N
Fülöp
Katalin
K
Dunkel
Petra
P
Gyires
Klára
K
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D054833:Isoindoles / Q000494:pharmacology; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D010109:Oxymetazoline / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017661:Receptors, Presynaptic / Q000187:drug effects*; D013270:Stomach / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007004:Hypoglycemic Agents; D007093:Imidazoles; D007328:Insulin; D054833:Isoindoles; D018721:Muscarinic Agonists; D017661:Receptors, Presynaptic; D010109:Oxymetazoline; D002217:Carbachol; D003000:Clonidine; D011224:Prazosin; C072125:BRL 44408