Summary
Experiments on saponin-permeabilized bovine and porcine coronary arteries were performed to examine whether fluoride-induced contractile mechanisms are retained after permeabilization and whether they modulate muscle tension without a change in cytoplasmic Ca2+.
Fluoride induced reversible contractions in skinned coronary smooth muscle and shifted the apparent Ca2+-sensitivity of the contractile system to lower Ca2+ values. Force development to fluoride required exogenous ATP and a minimum Ca 2+ concentration (pCa < 8) of the bathing medium. Force development occurred when the concentration of free Ca2+ available to the contractile apparatus seemed to be sufficiently controlled by a Ca2+-EGTA buffering system. The effects of fluoride were enhanced by Al3+ and imitated by both guanylyl-imidodiphosphate and 4β-phorbol-12,13-dibutyrate which suggests the involvement of both GTP-binding protein(s) and of the C-kinase pathway. Under conditions of sufficiently controlled Ca2+ buffering, saponin-skinned arteries responded to histamine or carbachol with an increase in muscle tension which was inhibited by specific receptor blocking agents (diphenhydramine, atropine), and which required the presence of both exogenous ATP and a low concentration of Ca2+ (pCa 7) which per se did not result in a contractile response.
It is concluded that agents acting on different steps of membrane-associated signal transduction pathways are able to induce contractile responses of saponin-skinned vascular smooth muscle without a change in cytosolic Ca2+ concentration.
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The results have been partly presented at the 27th Meeting of the former Society of Pharmacology and Toxicology of the GDR, Berlin, January 1989
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Fermum, R., Kosche, D. & Möritz, K.U. Membrane-associated signal transduction modulates contractile responses to Ca2+ in saponin-skinned coronary smooth muscle. Naunyn-Schmiedeberg's Arch Pharmacol 343, 209–216 (1991). https://doi.org/10.1007/BF00168612
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DOI: https://doi.org/10.1007/BF00168612