H2-receptor activity

The histamine H2-receptor (359 amino acids) is best known for its effect on gastric acid secretion. Histamine H2-receptor activation, in conjunction with gastrin and acetylcholine from the vagus, potently stimulate acid secretion from parietal cells. High concentrations of histamine are also present in cardiac tissues and can stimulate positive chronotropic and inotropic effects via H2-receptor stimulation and activation of adenylyl... 

H2 receptor stimulation in mammalian cerebral cortex and hippocampus produces excitation by inhibition of Ca2+-activated K+ conductances (Table 14-2). This effect resembles that produced by activation of [3-adrenergic receptors in these areas and both are mediated by increases in the cAMP-PKA pathway [1], H2 receptor activation also facilitates depolarization by enhancing the IH current,... 

Histaminergic neurons can regulate and be regulated by other neurotransmitter systems. A number of other transmitter systems can interact with histaminergic neurons (Table 14-1). As mentioned, the H3 receptor is thought to function as an inhibitory heteroreceptor. Thus, activation of brain H3 receptors decreases the release of acetylcholine, dopamine, norepinephrine, serotonin and certain peptides. However, histamine may also increase the activity of some of these systems through H, and/or H2 receptors. Activation of NMDA, p opioid, dopamine D2 and some serotonin receptors can increase the release of neuronal histamine, whereas other transmitter receptors seem to decrease release. Different patterns of interactions may also be found in discrete brain regions. 

Helmut Haas and colleagues showed that, in hippocampal pyramidal neurons, H2-receptor stimulation potentiates excitatory signals by decreasing a Ca2+-activated K+ conductance, presumably via cAMP production [11], H2-receptor activation depolarizes thalamic relay neurons slightly, increasing markedly apparent membrane conductance, a response due to enhancement of the hyperpolarization-activated cation current lh [20],... 

Ach, HA, and gastrin stimulate acid secretion by activating specific receptors on the ba-solateral membrane of the parietal cell. Once bound to the respective G-protein-coupled receptor, second-messenger systems are activated. Ach and gastrin activate phospholipase C to catalyze the conversion of membrane-bound phospholipids to diacylglycerol and inositol triphosphate. The release of Ca from intracellular stores and the subsequent increase in cytoplasmic Ca + activates ATPase (proton pump). The binding of HA to the H2-receptor activates adenylate cyclase, resulting in an increase in cAMP, which activates the proton pump (11). 

FIGURE 2. Post-receptor events initiated by H2- and H,-receptor activation by histamine (HIS). Adenylate cyclase (AC) stimulation occurs directly via H2-receptor activation or possibly indirectly via a calmodulin-calmodulin binding protein complex. Membrane inositol phospholipid (IPL) hydrolysis to inositol trisphosphate (IP3) is triggered by phospholipase C (PC) activation following H,-receptor stimulation. 

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