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Relaxation of hormonally stimulated smooth muscular tissues by the 8-bromo derivative of cyclic GMP

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Summary

Substances that cause contraction or relaxation of smooth muscle have been shown to increase intracellular levels of cyclic GMP. Because of the unclear role of cyclic GMP in the control of smooth muscle tone, cyclic GMP derivatives were exogenously applied to various smooth muscle preparations and their effects on tissue tone were studied.

Whereas the basal tone of the rat ductus deferens was not affected by exogenous cyclic GMP or its dibutyryl or 8-bromo derivatives, the contractile responses of this tissue to noradrenaline and acetylcholine were depressed by preincubation with 10 μM 8-bromo cyclic GMP (Br-cGMP). The 8-bromo derivatives of 2′:3′-cyclic GMP, 5′-GMP and guanosine were without effects. Cyclic AMP levels were not changed by Br-cGMP. The frequency of oxytocin-stimulated rat uteri was also depressed by Br-cGMP (10 μM). In helical strips of rat and rabbit aortae, Br-cGMP (1–100 μM) caused a concentration-dependent, rapid decrease in noradrenaline-stimulated tissue tension. Br-2′:3′-cyclic GMP was ineffective. Noradrenaline-stimulated strips from hog spleen arteries were less sensitive to Br-cGMP than aortic tissue. In ductus deferentes and aortic strips stimulated by K+ at a depolarizing concentration, Br-cGMP caused less relaxation than under hormonal stimulation.

These findings support the concept that cyclic GMP is involved in the control of smooth muscle tone and that hormone- and drug-induced elevations of the cyclic GMP level can reduce contractile responses to neurotransmitters and hormones.

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Abbreviations

cGMP:

Guanosine 3′:5′-monophosphate, cyclic GMP

dibutyryl cGMP:

N2, 2′-O-dibutyryl guanosine 3′:5′-monophosphate

Br-cGMP:

8-bromo guanosine 3′:5′-monophosphate

Br-2′:3′-cGMP:

8-bromo guanosine 2′:3′-monophosphate

Br-GMP:

8-bromo guanosine 5′-monophosphate

Br-Guo:

8-bromo guanosine, Br-guanosine

cAMP:

adenosine 3′:5′-monophosphate, cyclic AMP

dibutyryl cAMP:

N6, 2′-O-dibutyryl adenosine 3′:5′-monophosphate

Br-cAMP:

8-bromo adenosine 3′:5′-monophosphate

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Authors and Affiliations

  1. Pharmakologisches Institut, Universität Heidelberg, Im Neuenheimer Feld, D-6900, Heidelberg, Federal Republic of Germany

    Klaus-Dieter Schultz, Eycke Böhme & Günter Schultz

  2. II. Physiologisches Institut, Universität Heidelberg, Im Neuenheimer Feld, D-6900, Heidelberg, Federal Republic of Germany

    Volker A. W. Kreye

Authors
  1. Klaus-Dieter Schultz
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  2. Eycke Böhme
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  3. Volker A. W. Kreye
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  4. Günter Schultz
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Additional information

This work was supported by grants from the Deutsche Forschungsgemeinschaft. Preliminary reports were presented (Schultz, 1977b; Schultz et al., 1978).

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Schultz, KD., Böhme, E., Kreye, V.A.W. et al. Relaxation of hormonally stimulated smooth muscular tissues by the 8-bromo derivative of cyclic GMP. Naunyn-Schmiedeberg's Arch. Pharmacol. 306, 1–9 (1979). https://doi.org/10.1007/BF00515586

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