TY - JOUR
T1 - High-affinity binding of [3H]doxepin to histamine H1-receptors in rat brain
T2 - Possible identification of a subclass of histamine H1-receptors
AU - Taylor, John E.
AU - Richelson, Elliott
PY - 1982/3/12
Y1 - 1982/3/12
N2 - The binding of the radioactively labeled tricyclic antidepressant, [3H]doxepin, to rat brain tissie was examined. Scatchard plots of specific [3H]doxepin binding indicated the presence of two distinct binding sites. The equilibrium dissociation constant (KD) of the high-affinity site was 0.020 nM with a maximal binding capacity (Bmax) of 13.7 fmol/mg protein. The corresponding values for the low-affinity site were 3.6 nM and 740 fmol/mg protein, respectively. The high-affinity site was sensitive to competition by pharmacologically relevant concentrations of histamine H1 antagonists such as pyrilamine (KD = 1.0 nM), diphenhydramine (KD = 20 nM), d-chlorpheniramine (KD = 1.7 nM), and 1-chlorpheniramine (KD = 97 nM). The Bmax for [3H]doxepin binding in the high-affinity H1-receptor, however, was approximately 10% of the Bmax obtained using [3H]pyrilamine to label the H1-receptor. Various tricyclic antidepressants were very potent inhibitors at the high-affinity [3H]doxepin site. Their potencies, however, did not correlated with their potencies previously reported for the H1-receptor. The regional distribution of [3H]doxepin high-affinity sites correlated with the known distribution of H1-receptors in the rat brain. These results suggest that [3H]doxepin is binding to a subclass of histamine H1-receptors.
AB - The binding of the radioactively labeled tricyclic antidepressant, [3H]doxepin, to rat brain tissie was examined. Scatchard plots of specific [3H]doxepin binding indicated the presence of two distinct binding sites. The equilibrium dissociation constant (KD) of the high-affinity site was 0.020 nM with a maximal binding capacity (Bmax) of 13.7 fmol/mg protein. The corresponding values for the low-affinity site were 3.6 nM and 740 fmol/mg protein, respectively. The high-affinity site was sensitive to competition by pharmacologically relevant concentrations of histamine H1 antagonists such as pyrilamine (KD = 1.0 nM), diphenhydramine (KD = 20 nM), d-chlorpheniramine (KD = 1.7 nM), and 1-chlorpheniramine (KD = 97 nM). The Bmax for [3H]doxepin binding in the high-affinity H1-receptor, however, was approximately 10% of the Bmax obtained using [3H]pyrilamine to label the H1-receptor. Various tricyclic antidepressants were very potent inhibitors at the high-affinity [3H]doxepin site. Their potencies, however, did not correlated with their potencies previously reported for the H1-receptor. The regional distribution of [3H]doxepin high-affinity sites correlated with the known distribution of H1-receptors in the rat brain. These results suggest that [3H]doxepin is binding to a subclass of histamine H1-receptors.
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U2 - 10.1016/0014-2999(82)90029-2
DO - 10.1016/0014-2999(82)90029-2
M3 - Article
C2 - 7067728
AN - SCOPUS:0020075170
SN - 0014-2999
VL - 78
SP - 279
EP - 285
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 3
ER -