The autacoid and neurotransmitter histamine activates the H(1) G protein-coupled receptor (GPCR) to stimulate predominantly phospholipase C (PLC)/inositol phosphate (IP) signaling and, to a lesser extent, adenylyl cyclase (AC)/cAMP signaling in a variety of mammalian cells and tissues, as well as H(1)-transfected clonal cell lines. This study reports that two novel H(1) receptor ligands develop...

In exaggerated pain states, the activated astrocytes release several signalling molecules involved in cellular mechanisms of chronic pain. Among them, nerve growth factor (NGF) and interleukin (IL)-1β are both recognized as potent algogens. We previously showed that histamine is a potent stimulator of NGF production in rat cortical astrocytes in primary culture. Since histamine and IL-1β have c...

The histamine H3 receptor agonist (R)alpha-methylhistamine (MeHA) inhibited, in a nanomolar range, basal and carbachol-stimulated inositol phosphate formation in the human gastric tumoral cell line HGT1-clone 6. The inhibition was reversed by micromolar concentrations of the histamine H3 receptor antagonist thioperamide and was sensitive to cholera or pertussis toxin treatment. Using [3H]N alph...

Previous studies revealed that phenylhistamines and histaprodifens possess higher potency and affinity at guinea pig histamine H(1)-receptor (gpH(1)R) than at human histamine H(1)-receptor (hH(1)R). However, we recently identified an imidazolylpropylguanidine [N(1)-(3-cyclohexylbutanoyl)-N(2)-[3-(1H-imidazol-4-yl)-propyl]guanidine (UR-AK57)] with higher potency and efficacy at hH(1)R compared w...

Platelet-activating factor (PAF) may be an important mediator of allergic rhinitis. In the present study we evaluated the effectiveness of a recently described PAF antagonist (ABT-491) in rat and guinea pig models of allergic rhinitis. PAF, when perfused through the nasal passages of anesthetized Brown Norway rats, provoked an acute increase, measured as dye leakage, in nasal vascular permeabil...

Antihistamines, more formally termed H1 receptor antagonists, are well known to exert sedative effects in humans, yet their locus and mechanism of action in the human brain remains unknown. To better understand this phenomenon, the effects of histamine upon human cortical neurons were studied using intracellular recordings in brain slices maintained in vitro. Bath application of 50 microM hista...

One mechanism of histamine-mediated inhibition of the immune response in man is to activate T suppressor cells that bear the Leu 2 (OKT8) marker. The current study was undertaken to characterize the histamine-induced suppressor cell using a monoclonal antibody (9.3) shown previously to distinguish cytotoxic T cells from antigen-specific suppressor T cells. Leu 2+ cells isolated from peripheral ...

Five groups of ten female guinea-pigs were passively sensitized against ovalbumin (OA) (n = 9) or control guinea-pig serum (n = 1). 24 h later, they received mepyramine (0.5 mg/kg, i.p.) and 30 min later inhaled aerosols of: (A) OA (2 in 0.9% saline, 8 min, n = 4/9); (B) saline (40 min, n = 4/9); (C) LPS (40 min, Escherichia coli 0111:B4, 150 ng/kg in PBS, n = 1/9); and (D) the control animal w...

Splice products of the Kiss1 protein (kisspeptins) have been shown to be involved in a diverse range of functions, including puberty, metastasis and vasoconstriction in large human arteries. Circulating Kisspeptin-10 (Kp-10) plasma levels are low in normal individuals but are elevated during various disease states as well as pregnancy. Here, we investigated the potential of Kp-10, the shortest ...

The synergism between H1- and H2-receptors in the histamine-induced stimulation of cAMP accumulation was studied in slices from guinea pig hippocampus. Since H1-receptors appear to be coupled to the phosphatidylinositol cycle, the participation of the two branches of the cycle in this synergism was assessed by using phorbol esters and/or by removing Ca2+ from the external medium. The protein ki...