TY - JOUR
T1 - Alpha-noradrenergic receptor binding in mammalian brain
T2 - Differential labeling of agonist and antagonist states
AU - Greenberg, David A.
AU - U'Prichard, David C.
AU - Snyder, Solomon H.
N1 - Funding Information:
Research was supported by USPHS grant MH-18501, a Research Scientist Development Award, MH-31128 (to S,H,S,), and USPHS Fellowship Award, MH-05105 (to D, U'P,) .
PY - 1976/7/1
Y1 - 1976/7/1
N2 - [3H]Clonidine, a α-noradrenergic agonist, and [3H]WB-4101, a benzodioxan derivative α-antagonist, bind with high affinity and selectivity to membranes of rat brain in a fashion indicating that they label postsynaptic α-noradrenergic receptors. Binding for both ligands is saturable with KD values of 5 nM and 0.6 nM respectively for clonidine and WB-4101. The relative affinities of a series of phenylethylamines for binding sites corresponds well with their relative influences at α-receptors. Binding of both [3H]-ligands is stereoselective with about a 50 fold preference for (-)-norepinephrine. Of a series of ergot alkaloids, only those with known α-receptor activity have high affinities for the binding sites. Binding does not involve pre-synaptic norepinephrine nerve endings, because after an 80% depletion of endogenous norepinephrine by treatment with 6-hydroxydopamine, no decrease can be detected in [3H]clonidine and [3H]WB-4101 binding. α-Agonists have much higher affinities for [3H]clonidine than [3H]WB-4101 sites, while the reverse holds true for α-antagonists. Mixed agonist-antagonist ergots have similar affinities for binding of the two [3H]ligands. These data suggest that [3H]clonidine and [3H]WB-4101 respectively label distinct agonist and antagonist states of the α-receptor.
AB - [3H]Clonidine, a α-noradrenergic agonist, and [3H]WB-4101, a benzodioxan derivative α-antagonist, bind with high affinity and selectivity to membranes of rat brain in a fashion indicating that they label postsynaptic α-noradrenergic receptors. Binding for both ligands is saturable with KD values of 5 nM and 0.6 nM respectively for clonidine and WB-4101. The relative affinities of a series of phenylethylamines for binding sites corresponds well with their relative influences at α-receptors. Binding of both [3H]-ligands is stereoselective with about a 50 fold preference for (-)-norepinephrine. Of a series of ergot alkaloids, only those with known α-receptor activity have high affinities for the binding sites. Binding does not involve pre-synaptic norepinephrine nerve endings, because after an 80% depletion of endogenous norepinephrine by treatment with 6-hydroxydopamine, no decrease can be detected in [3H]clonidine and [3H]WB-4101 binding. α-Agonists have much higher affinities for [3H]clonidine than [3H]WB-4101 sites, while the reverse holds true for α-antagonists. Mixed agonist-antagonist ergots have similar affinities for binding of the two [3H]ligands. These data suggest that [3H]clonidine and [3H]WB-4101 respectively label distinct agonist and antagonist states of the α-receptor.
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U2 - 10.1016/0024-3205(76)90375-1
DO - 10.1016/0024-3205(76)90375-1
M3 - Article
C2 - 7724
AN - SCOPUS:0017159337
SN - 0024-3205
VL - 19
SP - 69
EP - 76
JO - Life Sciences
JF - Life Sciences
IS - 1
ER -