2.2 H1R and neural excitability
The human H1R gene is located on chromosome 3, which encodes a member of
the 7-transmembrane, G-protein-associated receptor family (486-491
amino-acids). H1R is coupled with Gq/11 protein and phospholipase C,
which in turn hydrolyses phosphatidyl-4, 5-biphosphate to form second
messenger, diacylglycerol (DAG) and phosphatidyl inositol-4,
5-biphosphate (IP3) (Leurs, Traiffort, Arrang,
Tardivel-Lacombe, Ruat & Schwartz, 1994). DAG activates phosphokinase C
(PKC), which in turn induces mitogen-activated protein kinase (MAPK)
activation, which involves in neuron synaptic plasticity (Yamamoto et
al., 2012). The DAG and IP3 promote calcium release from
the endoplasmic reticulum into the cytoplasm. In addition, H1R
activation subsequently leads to formation of arachidonic acid (AA) and
cyclic guanosine monophosphate (cGMP). The H1R is widely distributed in
the brain, including thalamus, cortex, basal forebrain, raphe nuclei,
hypothalamus, septal nuclei, amygdala, hippocampus, locus corelus,
nucleus accumbens, and nucleus tractus solitaries as well as cerebellum.
The central H1R is mainly corresponding for the side effects of
antihistamine drugs.
Most of H1R mediates either excitatory or inhibitory response of
histamine in neurons, depending on different brain regions. For example,
through H1R, histamine elicits neuronal excitability in the ventromedial
hypothalamus and GABAergic neurons in both substantia nigra and ventral
tegmental area, and the K+ channel is involved in that
(Korotkova, Haas & Brown, 2002; Zhou, Lee, Devidze, Zhang, Kow &
Pfaff, 2007). However, H1R also negatively regulate the neuronal
excitability. For instance, H1R decreases cell excitability of
hippocampal pyramidal neurons through activation of K+channels by increase of Ca2+ (Selbach, Brown & Haas,
1997). Similarly, H1R antagonist led to membrane potential
depolarization in superior cervical ganglion neurons via inhibiting
KCNQ/M K+ channel (Liu, Zhang, Wang, Zhang & Zhang,
2008).