Functional Analysis Of Histamine Receptor Subtypes Involved In Endothelium‐Mediated Relaxation Of The Human Uterine Artery

Abstract

1. This work was designed to introduce human uterine arteries as a new model for cardiovascular research. Advantages of this model include considerable availability of tissue because of the appearance of uterus myomatosus in post-menopausal women who undergo surgery and the chance to work on dysfunctional and healthy vessels. 2. Histamine evoked relaxation of the uterine artery that was prevented by removal of the endothelium or by the presence of N(G)-nitro-L-arginine. 3. Receptor antagonists for histamine H(1) (mepyramine) and H(2) (ranitidine) receptors increased the EC(50) of histamine by 112- and 67-fold, respectively. 4. Remarkably, isolated uterine arteries could be stored in incubators for 5 days without any change in contractility to phenylephrine and endothelium-dependent relaxation to acetylcholine and histamine. 5. Endothelial cells could be isolated and cultured in high purity, as demonstrated by histochemical staining of factor VIII, low CD45-RO for macrophages and no smooth muscle alpha-actin. In addition, cultured human uterine artery endothelial cells could be used for single cell Ca(2+) measurements. 6. In agreement with our findings in the intact vessel, histamine-initiated elevation of the intracellular free Ca(2+) concentration was reduced in the presence of mepyramine and ranitidine by 59 and 55%, respectively. 7. These data indicate that, in the human uterine artery, H(1) and H(2) receptors are involved in histamine-induced endothelium-dependent relaxation that is mediated by nitric oxide. 8. In addition, this vessel can be stored for possible virus-mediated gene expression for 5 days without any loss of reagibility. 9. Finally, endothelial cells can be isolated and cultured from the human uterine artery and maintain their reactivity to histamine in culture.

Histamine H2 Receptor Trafficking: Role of Arrestin, Dynamin, and Clathrin in Histamine H2 Receptor Internalization

“…Four distinct receptor subtypes (H1, H2, H3, and H4) belonging to the large family of G protein-coupled receptors (GPCRs) mediate histamine biological effects (Simons, 2004). The histamine H2 receptor (H2r) subserves hypotension, flushing, headache, increased gastric acid production, and enhanced vascular permeability (Sachs et al, 2002;Spitaler et al, 2002). By coupling to Gs, H2r triggers adenylyl cyclase activation and subsequent rapid cAMP accumulation (Hill, 1990).…”

Histamine induces activation of protein kinase D that mediates tissue factor expression and activity in human aortic smooth muscle cells

“…In particular, histamine has been reported to stimulate vascular wall permeability and endothelial dysfunction (21,26). Histamine also induces expression and secretion of various cytokines and chemokines (4,11).…”

“…As a potent inflammatory molecule, histamine increases blood vessel permeability and endothelial dysfunction (21,26) and induces relaxation (15,36) and constriction (13) of blood vessels. Through the cross talk between calcium flow and mitogen-activated protein kinase (MAPK) induction, histamine may be a risk factor for hypertension (5).…”

Histamine and Antihistamines / Histamin i antihistamini

“…Hypotension, tachycardia, flushing and headache occur through both the H1 and H2 receptors (55), whereas irritation of the skin in the form of itching and nasal congestion can be caused by the activation of H1 and H3 receptors (56,57). The role of histamine can be discussed also as a stimulatory signal for the production of cytokines and the expression of cell adhesion molecules in the latephase of allergic reaction (55,56,58,59).…”