Effects of a phorbol ester on rat aortic contraction and calcium influx in the presence and absence of BAY k 8644

PKCδ Mediates Testosterone-induced Increases in Coronary Smooth Muscle Cav1.2

“…In the rat aorta, estrogen has been identified as the primary mediator of sex differences in vascular reactivity and PKC␣, -␦, and -expression, with no effect of testosterone (17,22). However, in our porcine model, castration reduced, and testosterone replacement abrogated, coronary PKC␦ protein levels.…”

Eicosanoid‐induced Ca2+ release and sustained contraction in Ca2+‐free media are mediated by different signal transduction pathways in rat aorta

“…The effect of ,-TPA seems to be specific, since x-TPA, the biologicallyinactive isomer, did not affect the IP3 contents. It is well known that stimulated PIP2 breakdown mediated by activation of Ca2+ mobilizing receptors is inhibited by short-term treatment with active phorbol esters in many cell types (Orellana et al, 1985;Leeb-Lundberg et al, 1985;Litten et al, 1987;Slivka & Insel, 1988;Kaya et al, 1989;Chardonnens et al, 1990), including vascular smooth muscle cells (Roth et al, 1986;Reynolds et al, 1989;Araki et al, 1989). Our results showing that the 60-min treatment with P-TPA reduced the increased production of IP3 by PGF2, and U46619 are consistent with these reports, and suggest that the IP3-and DG-mediated responses to these eicosanoids should be diminished by prior treatment with the phorbol ester.…”

“…This was followed by a small, sustained contraction where [Ca2+]i was reduced to the basal level (Hisayama et al, 1990). The PGF2.-like actions are shared by endothelin-1 (Huang et al, 1990a (Orellana et al, 1985;Leeb-Lundberg et al, 1985;Roth et al, 1986;Litten et al, 1987;Slivka & Insel, 1988;Kaya et al, 1989;Araki et al, 1989). This providues us with a possible method of addressing this point, i.e., to learn which of the functional response(s) could be induced by the PIP2 breakdown reaction.…”

“…Activation of Ca2"-mobilizing receptors, has been shown to stimulate PIP2 breakdown, catalyzed by phospholipase C. This reaction results in an increased formation of inositol 1,4,5-trisphosphate (1P3) and diacylglycerol (DG), which it has been suggested, contributes to vascular smooth muscle contraction by releasing Ca2+ from the sarcoplasmic reticulum (SR; Berridge, 1989), stimulating Ca2+ entry (Litten et al, 1987) and sensitizing contractile apparatus by activating protein kinase C (PKC; Rasmussen et al, 1987;Ruzycky & Morgan, 1989;Karaki, 1989). One approach to monitor the IP3-induced intracellular Ca2+ release and the PKC-mediated increased sensitivity of contractile elements is to study the muscle responses to receptor agonists under Ca2+-free conditions.…”

“…Keywords: Vascular smooth muscle; prostaglandin F2CC; U46619; calcium; fura-2; Ca stores; protein kinase C; phorbol ester; inositol trisphosphate (Litten et al, 1987) and sensitizing contractile apparatus by activating protein kinase C (PKC; Rasmussen et al, 1987;Ruzycky & Morgan, 1989;Karaki, 1989 (Orellana et al, 1985;Leeb-Lundberg et al, 1985;Roth et al, 1986;Litten et al, 1987;Slivka & Insel, 1988;Kaya et al, 1989;Araki et al, 1989). This providues us with a possible method of addressing this point, i.e., to learn which of the functional response(s) could be induced by the PIP2 breakdown reaction.…”