Biomedical Engineering Reference
In-Depth Information
17
Histamine Receptors
Iwan de Esch, Henk Timmerman, and Rob Leurs
CONTENTS
17.1 Introduction ......................................................................................................................... 283
17.2 The Histamine H
1
Receptor: Molecular Aspects and Selective Ligands............................ 284
17.2.1 Molecular Aspects of the Histamine H
1
Receptor Protein .................................... 284
17.2.2 H
1
Receptor Agonists............................................................................................. 284
17.2.3 H
1
Receptor Antagonists........................................................................................ 285
17.2.4 Therapeutic Use of H
1
Receptor Ligands............................................................... 287
17.3 The Histamine H
2
Receptor: Molecular Aspects and Selective Ligands ........................... 287
17.3.1 Molecular Aspects of the Histamine H
2
Receptor Protein .................................... 287
17.3.2 H
2
Receptor Agonists............................................................................................. 287
17.3.3 H
2
Receptor Antagonists........................................................................................ 288
17.3.4 Therapeutic Use of H
2
Receptor Ligands .............................................................. 289
17.4 The Histamine H
3
Receptor: Molecular Aspects and Selective Ligands ........................... 290
17.4.1 Molecular Aspects of the Histamine H
3
Receptor Protein .................................... 290
17.4.2 Histamine H
3
Receptor Agonists ........................................................................... 291
17.4.3 Histamine H
3
Receptor Antagonists ...................................................................... 291
17.4.4 Therapeutic Use of Histamine H
3
Receptor Ligands............................................. 294
17.5 The Histamine H
4
Receptor: Molecular Aspects and Selective Ligands............................ 294
17.5.1 Molecular Aspects of the Histamine H
4
Receptor Protein .................................... 294
17.5.2 Histamine H
4
Receptor Agonists ........................................................................... 294
17.5.3 Histamine H
4
Receptor Antagonists ...................................................................... 295
17.5.4 Therapeutic Use of Histamine H
4
Receptor Ligands............................................. 296
17.6 Concluding Remarks........................................................................................................... 296
Further Readings............................................................................................................................ 297
17.1 INTRODUCTION
Histamine is both an aminergic neurotransmitter and a local hormone and plays major roles in the
regulation of several (patho) physiological processes. In biological systems histamine is synthesized
from l-histidine by histidine-decarboxylase (HDC, Scheme 17.1). In the brain (where histamine
acts as a neurotransmitter) the synthesis takes place in restricted populations of neurons that are
located in the tuberomammillary nucleus of the posterior hypothalamus. These neurons project to
most cerebral areas and have been implicated in several brain functions (e.g., sleep/wakefulness,
hormonal secretion, cardiovascular control, thermoregulation, food intake, and memory formation).
In peripheral tissues (where histamine acts as a local hormone), the compound is stored in mast cells,
eosinophils, basophils, enterochromafi n cells, and probably also in some specii c neurons. Once
released, histamine is rapidly metabolized via N-methylation of the imidazole ring by the enzyme
histamine
N
-methyltransferase (HMT) and by the oxidation of the amine function by diamine oxi-
dase (DAO, Scheme 17.1).
283
