Endogenous imidazoline receptor ligands relax rat aorta by an endothelium-dependent mechanism. 2003

Ian F Musgrave, and Andrea Van Der Zypp, and Mathew Grigg, and Colin J Barrow
Department of Clinical and Experimental Pharmacology, University of Adelaide, Adelaide 5005, Australia. ian.musgrave@adelaide.edu.au

Agmatine and harmane have been proposed as endogenous ligands of imidazoline receptors. Agmatine has been reported to activate nitric oxide synthetase (NOS) in endothelial cells, so we sought to determine if agmatine or harmane and an analogue of harmane, propyl harmane, produced vasodilatation through an endothelium-dependent mechanism. The experiments were performed in endothelium-denuded and intact rat aortic rings preconstricted with phenylephrine (0.1 microM). Agmatine (0.3-1000 microM), harmane, and propyl harmane (0.3-100 microM) relaxed endothelium-intact rings in a concentration-dependent manner. Removal of endothelium inhibited the relaxant effect of agmatine, harmane, and propyl harmane. The NOS inhibitor L-NIO (100 microM) inhibited the relaxant effect of agmatine and harmane. The I(1)-receptor antagonist AGN (100 microM) partly inhibited the effect of harmane but not that of agmatine. These results suggest that the endogenous imidazoline ligands are capable of stimulating NOS largely by an I(1)-receptor-independent mechanism.

UI MeSH Term Description Entries
D008024 Ligands A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed) Ligand
D008297 Male Males
D010656 Phenylephrine An alpha-1 adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent. (R)-3-Hydroxy-alpha-((methylamino)methyl)benzenemethanol,Metaoxedrin,Metasympatol,Mezaton,Neo-Synephrine,Neosynephrine,Phenylephrine Hydrochloride,Phenylephrine Tannate,Neo Synephrine,Tannate, Phenylephrine
D011955 Receptors, Drug Proteins that bind specific drugs with high affinity and trigger intracellular changes influencing the behavior of cells. Drug receptors are generally thought to be receptors for some endogenous substance not otherwise specified. Drug Receptors,Drug Receptor,Receptor, Drug
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004730 Endothelium, Vascular Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components. Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D006247 Harmine Alkaloid isolated from seeds of PEGANUM HARMALA; ZYGOPHYLLACEAE. It is identical to banisterine, or telepathine, from Banisteria caapi and is one of the active ingredients of hallucinogenic drinks made in the western Amazon region from related plants. It has no therapeutic use, but (as banisterine) was hailed as a cure for postencephalitic PARKINSON DISEASE in the 1920's. 9H-Pyrido(3,4-b)indole, 7-methoxy-1-methyl-,Banisterine,Leucoharmine,Telepathine,Yageine
D000376 Agmatine Decarboxylated arginine, isolated from several plant and animal sources, e.g., pollen, ergot, herring sperm, octopus muscle. 1-Amino-4-guanidinobutane,4-(Aminobutyl)guanidine,1 Amino 4 guanidinobutane
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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