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Sensitivity to cyclic nucleotides and to Aspirin® of the kininogen-consuming system activated by adrenaline or carbamylcholine in rat blood

  • Histamine and Kinins
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Abstract

The activation by carbamylcholine of a kinin-forming system in rat blood in vivo or in vitro has been compared with that caused by adrenaline. After showing that free kinins were actually released into the circulation of the carbamylcholine-treated rat, experimentally induced changes in carbamylcholine or adrenaline activity were followed by measuring alterations in kinin precursor (kininogen) levels in plasma. Carbamylcholine was effective at 1.6–4.8 μg/kg in the intact animal and optimal at 10−8 M in oxalated rat blood in vitro. Aspirin®, 10 mg/kg or 5×10−4 M, inhibited the action of carbamylcholine and of adrenaline on kininogen. Salicylate or Indomethacin at similar levels were ineffective. N6-,2′-O-dibutyryl-cyclic-3′,5′ adenosine monophosphate (diBu-cAMP) 2×10−5 M, suppressed kininogen consumption in vitro; this inhibition could be overcome by 8-bromo-3′–5′-cyclic guanosine monophosphate (8-Br-cGMP), 10−4 M. This compound potentiated the effect of adrenaline in the absence of diBu-cAMP. The inhibitory effect of Aspirin® was decreased by 8-Br-cGMP. The action of autonomic effector drugs on kininogen consumption may be mediated by changes in the cAMP/cGMP ratio in circulatory target cells. The action of Aspirin® may affect this system since it was partially overcome by 8-Br-cGMP. Since it was not reproduced by salicylate but could be mimicked by acetic anhydride, it most probably involves the transfer of the acetyl group of the drug to an as yet unknown acceptor cell protein. This moiety does not seem to be involved in prostaglandin-synthesis since Indomethacin, a very effective inhibitor of this process, failed to inhibit the action of either adrenaline or carbamylcholine on rat blood kininogen.

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  1. Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, 14.100, Ribeirão Preto, S.P., Brazil

    A. M. Rothschild & A. Castania

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  1. A. M. Rothschild
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  2. A. Castania
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Rothschild, A.M., Castania, A. Sensitivity to cyclic nucleotides and to Aspirin® of the kininogen-consuming system activated by adrenaline or carbamylcholine in rat blood. Agents and Actions 8, 132–138 (1978). https://doi.org/10.1007/BF01972415

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