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Inositol-1,4,5-trisphosphate mass content in isolated perfused rat heart during alpha-1-adrenoceptor stimulation

  • Part I: Cardiac Development and Regulation
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Abstract

Inositol-1,4,5-trisphosphate (IP3) has been proposed to be a second messenger in response to alpha-1-adrenoceptor stimulation also in myocardial cells. We studied the effect of alpha-1-adrenoceptor stimulation (5 × 10−5 mol/l phenylephrine or 5 × 10−5 mol/l noradrenaline both in the presence of 10−6 mol/l timolol) on IP3 mass content in isolated perfused rat hearts. IP3 content was determined by a specific receptor-binding assay-kit (TRK 1000, Amersham) after validating the method. For comparison also the effect of muscarinic stimulation (10−4 mol/l carbachol in the presence of 10−6 mol/l timolol) on IP3 content was measured in corresponding preparations. A basal IP3 level of about 75 pmol/mg protein was found. There were no prominent effects of alpha-1-adrenoceptor stimulation on total IP3 content in isolated perfused rat hearts. Phenylephrine gave a statistically significant increase of about 40% at 1/4 min and a statistically significant decrease of about 25% at 4 min after start of exposure. Noradrenaline, however, gave no statistically significant change of IP3 at the time-points studied. Muscarinic stimulation caused a slight, statistically insignificant, increase of IP3 at 1/4 min. The results are compatible with an assumption that agonist stimulation evokes a localized increase of IP3 which may be masked by a relatively high total IP3 mass content. The IP3 peak after phenylephrine coincided with the early positive inotropic phase of the response reported earlier in perfused rat hearts for alpha-1-adrenoceptor stimulation by phenylephrine. Although this might be compatible with a role for IP3 in this early and transient phase, a mediator function of IP3 in the inotropic response is not established.

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  1. Sigrid Hanem

    Present address: Department of Anaestesiology, Rikshospitalet, N-0027, Oslo, Norway

Authors and Affiliations

  1. Department of Pharmacology, University of Oslo, P.O. Box 1057 Blindern, N-0316, Oslo, Norway

    Sigrid Hanem, Mette Enger, Tor Skomedal & Jan-Bjørn Osnes

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Hanem, S., Enger, M., Skomedal, T. et al. Inositol-1,4,5-trisphosphate mass content in isolated perfused rat heart during alpha-1-adrenoceptor stimulation. Mol Cell Biochem 163, 167–172 (1996). https://doi.org/10.1007/BF00408654

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