Faculty Opinions recommendation of Small mouse cholangiocytes proliferate in response to H1 histamine receptor stimulation by activation of the IP3/CaMK I/CREB pathway.

AbstractThe inflammatory reaction influences the deposition of collagen within wound granulation tissue. The aim of the present study is to determine whether histamine acting directly on myofibroblasts derived from wound granulation tissue may influence collagen deposition. It also identifies the histamine receptor involved in this process. The experiments were carried out on cells isolated from the granulation tissue of a wound model (a polypropylene net inserted subcutaneously to rats) or intact rat skin. Collagen content was measured following the addition of different concentrations of histamine and treatment with histamine receptor antagonists (ketotifen – H1 inhibitor, ranitidine – H2 inhibitor) and a histamine receptor H1 agonist (2-pyridylethylamine dihydrochloride).The cells were identified as myofibroblasts: alpha-smooth muscle actin, vimentin, and desmin positive in all experimental conditions. Histamine increased the collagen level within both cell cultures, i.e., those isolated from granulation tissue or intact skin. It did not, however, influence the expression of either the collagen type I or III genes within the cultured myofibroblasts. Histamine activity was reduced by ketotifen (the H1 receptor inhibitor) and increased by the H1 receptor agonist, as demonstrated by changes in the levels of collagen in the myofibroblast culture. Histamine increased collagen content within the cultures, acting directly on myofibroblasts via H1 receptor stimulation.

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Characterization of the histamine receptors in rabbit left atria

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y81-004 ◽

1981 ◽

Vol 59 (1) ◽

pp. 19-24 ◽

Cited By ~ 1

Author(s):

Alicia Polanin ◽

John H. McNeill

Keyword(s):

Left Atrial ◽

Histamine Receptor ◽

Histamine Receptors ◽

Receptor Blockade ◽

Inotropic Response ◽

Receptor Stimulation ◽

Inotropic Effects ◽

Receptor Antagonism ◽

Positive Inotropic Effects

The effects of selective histamine receptor analogs were studied in electrically paced rabbit left atria. Atrial tension was increased by histamine (an H1 and H2 agonist), 4-methylhistamine and impromidine (H2 agonists), and 2-pyridylethylamine (PEA) (an H1 agonist). The responses to histamine and impromidine were not altered by propranolol (1 × 10−7 M) or reserpine pretreatment. However, the responses to 4-methylhistamine and PEA were significantly decreased upon pretreatment with propranolol or reserpine. Promethazine pretreatment (H1 receptor blockade) antagonized the inotropic effects of histamine and PEA but had no effect on the responses to 4-methylhistamine or impromidine. Cimetidine pretreatment (H2 receptor antagonism) competitively blocked the positive inotropic effects of histamine, 4-methylhistamine, and impromidine. These results suggest that the left atrial inotropic response is mediated through H1 and H2 receptor stimulation.

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Suppression of inflammatory cell recruitment by histamine receptor stimulation in ischemic rat brains

European Journal of Pharmacology ◽

10.1016/j.ejphar.2006.11.020 ◽

2007 ◽

Vol 557 (2-3) ◽

pp. 236-244 ◽

Cited By ~ 30

Author(s):

Norihito Hiraga ◽

Naoto Adachi ◽

Keyue Liu ◽

Takumi Nagaro ◽

Tatsuru Arai

Keyword(s):

Inflammatory Cell ◽

Histamine Receptor ◽

Receptor Stimulation ◽

Cell Recruitment ◽

Inflammatory Cell Recruitment

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P2X4 Receptors Mediate Ca2+ Release from Lysosomes in Response to Stimulation of P2X7 and H1 Histamine Receptors

International Journal of Molecular Sciences ◽

10.3390/ijms221910492 ◽

2021 ◽

Vol 22 (19) ◽

pp. 10492

Author(s):

Sin-Lih Tan ◽

Muruj Barri ◽

Peace Atakpa-Adaji ◽

Colin W. Taylor ◽

Ewan St. John Smith ◽

...

Keyword(s):

Membrane Trafficking ◽

P2x7 Receptor ◽

Purinergic Receptor ◽

Histamine Receptor ◽

Receptor Activation ◽

Receptor Stimulation ◽

Inward Current ◽

P2x4 Receptors ◽

P2x7 Receptor Activation ◽

Stimulation Of

The P2X4 purinergic receptor is targeted to endolysosomes, where it mediates an inward current dependent on luminal ATP and pH. Activation of P2X4 receptors was previously shown to trigger lysosome fusion, but the regulation of P2X4 receptors and their role in lysosomal Ca2+ signaling are poorly understood. We show that lysosomal P2X4 receptors are activated downstream of plasma membrane P2X7 and H1 histamine receptor stimulation. When P2X4 receptors are expressed, the increase in near-lysosome cytosolic [Ca2+] is exaggerated, as detected with a low-affinity targeted Ca2+ sensor. P2X4-dependent changes in lysosome properties were triggered downstream of P2X7 receptor activation, including an enlargement of lysosomes indicative of homotypic fusion and a redistribution of lysosomes towards the periphery of the cell. Lysosomal P2X4 receptors, therefore, have a role in regulating lysosomal Ca2+ release and the regulation of lysosomal membrane trafficking.

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Small mouse cholangiocytes proliferate in response to H1 histamine receptor stimulation by activation of the IP3/CaMK I/CREB pathway

AJP Cell Physiology ◽

10.1152/ajpcell.00369.2007 ◽

2008 ◽

Vol 295 (2) ◽

pp. C499-C513 ◽

Cited By ~ 92

Author(s):

Heather Francis ◽

Shannon Glaser ◽

Sharon DeMorrow ◽

Eugenio Gaudio ◽

Yoshiyuki Ueno ◽

...

Keyword(s):

Histamine Receptor ◽

Camp Response Element Binding ◽

Camp Response Element ◽

Dependent Protein Kinase ◽

Element Binding Protein ◽

Intracellular Ca ◽

Dependent Protein ◽

Camp Levels ◽

Dependent Mechanism ◽

Creb Pathway

Cholangiopathies are characterized by the heterogeneous proliferation of different-sized cholangiocytes. Large cholangiocytes proliferate by a cAMP-dependent mechanism. The function of small cholangiocytes may depend on the activation of inositol trisphosphate (IP3)/Ca2+-dependent signaling pathways; however, data supporting this speculation are lacking. Four histamine receptors exist (HRH1, HRH2, HRH3, and HRH4). In several cells: 1) activation of HRH1 increases intracellular Ca2+ concentration levels; and 2) increased [Ca2+]i levels are coupled with calmodulin-dependent stimulation of calmodulin-dependent protein kinase (CaMK) and activation of cAMP-response element binding protein (CREB). HRH1 agonists modulate small cholangiocyte proliferation by activation of IP3/Ca2+-dependent CaMK/CREB. We evaluated HRH1 expression in cholangiocytes. Small and large cholangiocytes were stimulated with histamine trifluoromethyl toluidide (HTMT dimaleate; HRH1 agonist) for 24–48 h with/without terfenadine, BAPTA/AM, or W7 before measuring proliferation. Expression of CaMK I, II, and IV was evaluated in small and large cholangiocytes. We measured IP3, Ca2+ and cAMP levels, phosphorylation of CaMK I, and activation of CREB (in the absence/presence of W7) in small cholangiocytes treated with HTMT dimaleate. CaMK I knockdown was performed in small cholangiocytes stimulated with HTMT dimaleate before measurement of proliferation and CREB activity. Small and large cholangiocytes express HRH1, CaMK I, and CaMK II. Small (but not large) cholangiocytes proliferate in response to HTMT dimaleate and are blocked by terfenadine (HRH1 antagonist), BAPTA/AM, and W7. In small cholangiocytes, HTMT dimaleate increased IP3/Ca2+ levels, CaMK I phosphorylation, and CREB activity. Gene knockdown of CaMK I ablated the effects of HTMT dimaleate on small cholangiocyte proliferation and CREB activation. The IP3/Ca2+/CaMK I/CREB pathway is important in the regulation of small cholangiocyte function.

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