Norepinephrine release is reduced by I(1)-receptors in addition to alpha(2)-adrenoceptors.
In pithed spontaneous hypertensive rats, noradrenaline overflow was diminished by moxonidine even when alpha(2)-adrenoceptors were blocked quantitatively using phenoxybenzamine, suggesting an I(1)-receptor-mediated mechanism of noradrenaline release. This hypothesis was confirmed, since the noradrenaline overflow was (1) increased under alpha(2)-adrenoceptors blockade by the mixed I(1)/alpha(2)-antagonists efaroxan or idazoxan, (2) still reduced by moxonidine when both alpha(2)- and I(1)-receptors were blocked, and (3) diminished by agmatine after pretreatment with phenoxybenzamine, but not with AGN192403. An indirect ganglionic I(1)-receptor-mediated mechanism of noradrenaline release is supposed.
Raasch
Walter
W
Institute of Experimental and Clinical Pharmacology and Toxicology, University Clinic Schleswig-Holstein, Campus Lübeck, Germany. raasch@medinf.mu-luebeck.de
Jungbluth
Britta
B
Schäfer
Ulrich
U
Häuser
Walter
W
Dominiak
Peter
P
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000376:Agmatine / Q000494:pharmacology; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D001794:Blood Pressure / Q000502:physiology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D004558:Electric Stimulation; D006536:Heptanes / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism*; D019329:Idazoxan / Q000494:pharmacology; D007093:Imidazoles / Q000378:metabolism / Q000494:pharmacology; D054755:Imidazoline Receptors; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010643:Phenoxybenzamine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism
C098523:AGN 192403; D000317:Adrenergic alpha-Antagonists; D001572:Benzofurans; D001643:Bridged Bicyclo Compounds; D006536:Heptanes; D007093:Imidazoles; D054755:Imidazoline Receptors; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; C410887:imidazoline I1 receptors; D010643:Phenoxybenzamine; D000376:Agmatine; C043482:moxonidine; C062597:efaroxan; D009638:Norepinephrine; D019329:Idazoxan