AIMTo investigate the effect of selective H3 receptor agonist(R)-alpha-methylhistamine and antagonist thioperamide on the respiratory response in asthmatic guinea pigs respectively.

METHODSAnesthesized guinea pigs were prepared with a implanted intracerebroventricular (icv) cannula and instrumented for the measurement of respiratory rate (RR) and diaphragmatic electric activity (DA). Substance P-like immunoreactive (SP-LI) substances in lower respiratory tract were detected by immunohistochemical method. Brain histamine contents were measured by fluorometric determination.

RESULTS(1) Intravenous injection of ovalbumin caused tachypnea and significant decrease in DA magnitude. At the same time, SP-LI substances increased in trachea, bronchus and lung. (2) Administration of selective H3 receptor agonist (R)-alpha-methylhistamine (5 microg) icv immediately after i.v. ovalbumin could significantly ameliorate the changes in RR and DA induced by ovalbumin. In accordance, SP-LI substances in lower respiratory tract markedly decreased at 5 min and 10 min after (R)-alpha-methylhistamine microinjection. (3) Icv thioperamide (20 microg) caused a significant increase in RR and a decrease in DA. (4) Brain histamine contents increased in hypothalamus and cortex during asthma. After microinjection of thioperamide (20 microg) icv significant increase of histamine contents in hypothalamus and cortex was observed.

CONCLUSIONBrain histamine H3 receptors may be related to asthmatic respiratory responses.

Animals ; Asthma ; metabolism ; Brain ; metabolism ; Guinea Pigs ; Histamine Agonists ; pharmacology ; Histamine H3 Antagonists ; pharmacology ; Lateral Ventricles ; Male ; Methylhistamines ; pharmacology ; Muscle Contraction ; Piperidines ; pharmacology ; Receptors, Histamine H3 ; metabolism ; Substance P ; metabolism ; Trachea ; physiopathology

No abstract available.
Basophils* ; Histamine Release* ; Histamine*

No abstract available.
Capillaries* ; Histamine*

No abstract available.
Histamine* ; Pneumocytes*

No abstract available.
Histamine* ; Pruritus*

No abstract available.
Eosinophils* ; Histamine*

The following four possible pathways for itching sensation have been suggested by recent reports. 1) Histaminergic TRPV1-positive pathway: Although histamine-positive nerve fibers cannot strictly be classified as “itch specific” due to their excitation also by pure algogens (making them itch-selective), the existence of a subpopulation of nociceptors responsible for itching is strongly suggested. Moreover, the TRPV1-expressing neurons have been suggested to be the main sensors and mediators of itching. 2) Histaminergic TRPV1-negative pathway: The scratching behavior caused by itching was not different between capsaicin-pre-treated and vehicle-treated (control) mast cell-rich NC mice. This result suggests the existence of a capsaicin-insensitive (TRPV1-negative) histaminergic pathway. 3) Non-histaminergic PAR-2 pathway: Protease-activated receptor 2 (PAR-2) has been shown to play a role in the itching of atopic dermatitis (AD). The itch evoked by cowhage (a non-histaminergic pruritogen that activates PAR-2) is very similar in characteristics to the itch evoked by conditions such as AD. 4) Non-histaminergic serotonin (5-HT) pathway: 5-HT alone applied to the human skin evokes an itching sensation and has been suggested to be involved in the itching associated with pruritic diseases, such as polycythemia vera and cholestasis.
Pruritus ; Histamine

Interstitial cells of Cajal (ICCs) are the pacemaker cells in the gastrointestinal tract, and histamine is known to regulate neuronal activity, control vascular tone, alter endothelial permeability, and modulate gastric acid secretion. However, the action mechanisms of histamine in mouse small intestinal ICCs have not been previously investigated, and thus, in the present study, we investigated the effects of histamine on mouse small intestinal ICCs, and sought to identify the receptors involved. Enzymatic digestions were used to dissociate ICCs from small intestines, and the whole-cell patch-clamp configuration was used to record potentials (in current clamp mode) from cultured ICCs. Histamine was found to depolarize resting membrane potentials concentration dependently, and whereas 2-PEA (a selective H1 receptor agonist) induced membrane depolarizations, Dimaprit (a selective H2-agonist), R-alpha-methylhistamine (R-alpha-MeHa; a selective H3-agonist), and 4-methylhistamine (4-MH; a selective H4-agonist) did not. Pretreatment with Ca(2+)-free solution or thapsigargin (a Ca(2+)-ATPase inhibitor in endoplasmic reticulum) abolished the generation of pacemaker potentials and suppressed histamine-induced membrane depolarization. Furthermore, treatments with U-73122 (a phospholipase C inhibitor) or 5-fluoro-2-indolyl des-chlorohalopemide (FIPI; a phospholipase D inhibitor) blocked histamine-induced membrane depolarizations in ICCs. On the other hand, KT5720 (a protein kinase A inhibitor) did not block histamine-induced membrane depolarization. These results suggest that histamine modulates pacemaker potentials through H1 receptor-mediated pathways via external Ca2+ influx and Ca2+ release from internal stores in a PLC and PLD dependent manner.
Animals ; Carbazoles ; Cyclic AMP-Dependent Protein Kinases ; Dimaprit ; Domperidone ; Estrenes ; Gastric Acid ; Gastrointestinal Tract ; Hand ; Histamine ; Indoles ; Interstitial Cells of Cajal ; Intestine, Small ; Membrane Potentials ; Membranes ; Methylhistamines ; Mice ; Neurons ; Permeability ; Phospholipase D ; Pyridoxal ; Pyrroles ; Pyrrolidinones ; Thapsigargin ; Type C Phospholipases

To learn the differences between the structure-activity relationship and molecular vibration-activity relationship in the ligand-receptor interaction of the histamine receptor, 47 ligands of the histamine receptor were analyzed by structural similarity and molecular vibrational frequency patterns. The radial tree that was produced by clustering analysis of molecular vibrational frequency patterns shows its potential for the functional classification of histamine receptor ligands.
Histamine ; Ligands ; Receptors, Histamine ; Structure-Activity Relationship

No abstract available.
Anaphylaxis* ; Histamine Release* ; Histamine* ; Mast Cells*