TY - JOUR
T1 - Distinct α-noradrenergic receptors differentiated by binding and physiological relationships
AU - U'Prichard, David C.
AU - Snyder, Solomon H.
N1 - Funding Information:
We thank Mr. G. Mack for excellent technical assistance and Pamela Morgan manuscript preparation. Supported by USPHS grants Ma-18501 and DA-00266 sad grants of the Joha A. Bartford Foundation and the MclCnight Foundation.
PY - 1979/1/1
Y1 - 1979/1/1
N2 - In brain and peripheral tissues the α-noradrenergic agonists 3H-clonidine, 3H-epinephrine and 3H-norepinephrine label sites which are distinct from and do not interconvert with those labeled by the α-noradrenergic antagonist 3H-WB-4101 (2-([2', 6'-dimethoxy]-phenoxyethylamino) methylbenzodioxane). In general agonists have higher affinity for sites labeled by the 3H-agonists while antagonists prefer sites labeled by 3H-WB-4101, though ergots and the α-antagonist phentolamine have similar affinities for the two sites. Peripheral tissues vary in relative numbers of 3H-agonist and 3H-WB-4101 sites with heart and vas deferens having almost exclusively 3H-WB-4101 sites, the rabbit duodenum only 3H-agonist sites, while salivary gland, spleen and cerebral cortex display similar numbers of both sites. The two sites appear to be postsynaptic since 6-hydroxydopamine treatment does not reduce their numbers. In vas deferens, heart and spleen pharmacological potencies of α-agonists and antagonists correlate closely with affinities for 3H-WB-4101 but not 3H-clonidine sites, while potencies in rabbit duodenum correlate with affinities for 3H-clonidine but not 3H-WB-4101 sites. The correspondence of separate binding sites with distinctive patterns of physiological responses indicates the existence of two discrete types of postsynaptic α-receptors. We propose to designate sites labeled by WB-4101 as α-1 receptors and those labeled by 3H-clonidine, 3H-norepinephrine and 3H-epinephrine as α-2 receptors. Drug potencies at α-2 binding sites resemble their affinities for presynaptic α-noradrenergic autoreceptors.
AB - In brain and peripheral tissues the α-noradrenergic agonists 3H-clonidine, 3H-epinephrine and 3H-norepinephrine label sites which are distinct from and do not interconvert with those labeled by the α-noradrenergic antagonist 3H-WB-4101 (2-([2', 6'-dimethoxy]-phenoxyethylamino) methylbenzodioxane). In general agonists have higher affinity for sites labeled by the 3H-agonists while antagonists prefer sites labeled by 3H-WB-4101, though ergots and the α-antagonist phentolamine have similar affinities for the two sites. Peripheral tissues vary in relative numbers of 3H-agonist and 3H-WB-4101 sites with heart and vas deferens having almost exclusively 3H-WB-4101 sites, the rabbit duodenum only 3H-agonist sites, while salivary gland, spleen and cerebral cortex display similar numbers of both sites. The two sites appear to be postsynaptic since 6-hydroxydopamine treatment does not reduce their numbers. In vas deferens, heart and spleen pharmacological potencies of α-agonists and antagonists correlate closely with affinities for 3H-WB-4101 but not 3H-clonidine sites, while potencies in rabbit duodenum correlate with affinities for 3H-clonidine but not 3H-WB-4101 sites. The correspondence of separate binding sites with distinctive patterns of physiological responses indicates the existence of two discrete types of postsynaptic α-receptors. We propose to designate sites labeled by WB-4101 as α-1 receptors and those labeled by 3H-clonidine, 3H-norepinephrine and 3H-epinephrine as α-2 receptors. Drug potencies at α-2 binding sites resemble their affinities for presynaptic α-noradrenergic autoreceptors.
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U2 - 10.1016/0024-3205(79)90283-2
DO - 10.1016/0024-3205(79)90283-2
M3 - Article
C2 - 33313
AN - SCOPUS:0018345920
SN - 0024-3205
VL - 24
SP - 79
EP - 88
JO - Life Sciences
JF - Life Sciences
IS - 1
ER -