Positive Inotropic Effects of Imidazoline Derivatives Are Not Mediated via Imidazoline Binding Sites but α_1-Adrenergic Receptors

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Abstract

Imidazoline−binding sites are non−adrenergic receptors and classified into I<SUB>1</SUB>/I<SUB>2</SUB> subtypes.There is strong evidence that I<SUB>1</SUB>−binding sites, located in the rostro−ventrolateral medulla, are involved in regulation of blood pressure.However, less is known about the peripheral participation of I<SUB>1</SUB>−binding sites in cardiovascular reactions.Therefore, the aim of this study was to investigate whether specific imidazoline derivatives influence myocardial contractility and whether imidazoline binding sites are expressed in rat heart.Agmatine, clonidine and idazoxan failed to alter inotropy in left atria within the whole concentration range tested(1 nM−100μM), whereas cirazoline(1−100μM)and moxonidine(100μM)increase inotropy by about 20−30%.After pre−incubation with the α<SUB>1</SUB>−adrenoceptor antagonist prazosin, the cirazoline and moxonidine stimulated inotropy was antagonized, indicating more an α<SUB>1</SUB>−adrenergic and less an imidazoline binding site mediated mechanism.Radioligand−binding studies in membranes of left ventricles using [<SUP>3</SUP>H]−clonidine to specify I<SUB>1</SUB>−binding yielded K<SUB>D</SUB> values of 12.7μM, confirming the functional results of an absence of I<SUB>1</SUB>−binding sites in ventricles of rats.However, the existence of low affinity I<SUB>2</SUB>−binding sites determined by [<SUP>3</SUP>H]−idazoxan labeling could not be excluded since a K<SUB>D</SUB> of 0.5μM was calculated and since competition studies with guanabenz(K<SUB>i</SUB>=0.1μM), clonidine(K<SUB>i</SUB>=58.1μM)and moxonidine(K<SUB>i</SUB>=129μM)confirmed the specificity of the I<SUB>2</SUB>−binding.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 84(1), 1-6, 2000-09-01

    The Japanese Pharmacological Society

References:  35

Codes

  • NII Article ID (NAID)
    10008184906
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    00215198
  • NDL Article ID
    5525991
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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