High-affinity binding of [3H]doxepin to histamine H1-receptors in rat brain: Possible identification of a subclass of histamine H1-receptors

John E. Taylor, Elliott Richelson

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)279-285
Number of pages7
JournalEuropean Journal of Pharmacology
Volume78
Issue number3
DOIs
StatePublished - Mar 12 1982

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Doxepin
Histamine H1 Receptors
Brain
Chlorpheniramine
Pyrilamine
Tricyclic Antidepressive Agents
Histamine H1 Antagonists
Diphenhydramine
Proteins
Binding Sites

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

High-affinity binding of [3H]doxepin to histamine H1-receptors in rat brain : Possible identification of a subclass of histamine H1-receptors. / Taylor, John E.; Richelson, Elliott.

In: European Journal of Pharmacology, Vol. 78, No. 3, 12.03.1982, p. 279-285.

Research output: Contribution to journalArticle

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abstract = "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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