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I 1 Imidazoline Receptors Involved in Cardiovascular Regulation: Where Are We and Where Are We Going?
Author(s) -
BOUSQUET P,
GRENEY H,
BRUBAN V,
SCHANN S,
EHRHARDT JD,
MONASSIER L,
FELDMAN J
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1304.028
Subject(s) - imidazoline receptor , blood pressure , clonidine , receptor , alpha (finance) , antagonist , chemistry , pharmacology , rilmenidine , adrenergic receptor , alpha 2 adrenergic receptor , endocrinology , medicine , agonist , biology , biochemistry , construct validity , nursing , patient satisfaction
A bstract : Clonidine‐like drugs (hybrid drugs) reduce blood pressure by acting centrally at both a 2 ‐adrenergic receptors (a 2 AR) and I 1 receptors (I 1 R). Some attempts at cloning I 1 R have failed, probably because of the lack of selectivity of the ligands. Recently, compounds acting exclusively at I 1 R were synthesized: LNP 911, LNP509, and S23515. For example, LNP911 has a K d value of 1.7 nmol/L at I 1 R. LNP509 and S23515 reduce blood pressure when injected centrally in anesthetized animals, whereas S23757 behaves as an antagonist of hypotensive imidazolines. LNP509 reduces blood pressure even in genetically engineered mice lacking functional a 2 AR. An exclusive action at central I 1 R is therefore sufficient to modify blood pressure. With the help of drugs selective for I 1 R and a‐methylnoradrenaline, selective for a 2 AR, we showed that imidazoline and a 2 ‐adrenergic mechanisms interact synergistically in controlling the blood pressure. Such a synergism may explain the very powerful hypotensive effects of hybrid drugs. The new ligands selective for I 1 R will be very helpful to investigate the molecular features and the signaling system of I 1 R.