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  • Title: Effects of phorbol-12,13-dibutyrate and protein kinase C inhibitors on Mn(2+)-dependent norepinephrine-induced contractions involving increase in Mn2+ sensitivity in Ca(2+)-depleted vas deferens of the guinea pig.
    Author: Tsunobuchi-Ushijima H, Gomi Y.
    Journal: Gen Pharmacol; 1997 Oct; 29(4):591-5. PubMed ID: 9352308.
    Abstract:
    1. In Ca(2+)-depleted Mn(2+)-loaded vas deferens from the guinea pig (Mn-loaded preparations), norepinephrine (NE) induced a tonic contraction dose dependently without extracellular Ca2+ and Mn2+. 2. In the beta-escin skinned vas deferens, Mn2+ as well as Ca2+ induced contractions. Guanosine triphosphate and NE increased the sensitivity of contractile mechanisms to these divalent cations. 3. Phorbol-12,13-dibutyrate (PDBu) did not induce contractions in normal (Mn(2+)-unloaded Ca(2+)-contained) preparations, whereas it induced slow sustained contractions dose dependently in Mn-loaded preparations. Although cumulative applications of PDBu desensitized the preparations to this phorbol ester, the desensitization did not affect Mn(2+)-dependent NE-induced contractions. PDBu did not affect the dose-response relation of NE in Mn-loaded preparations. 4. Staurosporine (10-100 nM) preferentially inhibited NE-induced contractions in normal and in Mn-loaded preparations to that induced by K+ in normal preparations. However, bisindolylmaleimide I (1 microM) did not inhibit NE-induced contractions in normal and Mn-loaded preparations but abolished PDBu-induced contractions. 5. These results suggest that the NE-induced increase in the Mn2+ sensitivity of contractile mechanisms contributes to Mn(2+)-dependent NE-induced contractions, which may not involve the activation of protein kinase C.
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