Mechanisms of pinacidil-induced vasodilatation

Anabuki, Jun; Hori, Masaru; Ozaki, Hiroshi; Kato, Iwao; Karaki, Hideaki

doi:10.1016/0014-2999(90)94202-9

Cited by 30 publications

(18 citation statements)

References 27 publications

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“…The recent studies concerning vasoconstriction induced phorbol ester tend to support a role for protein kinase C in the change of Ca 2+ sensitiv ity of the contractile elements, although it fails to establish a clear link between a,-adreno ceptors, protein kinase C and myofilament (23). Nishimura et al (23) provided direct evidence that the activation of G-protein by an ai adrenoceptor agonist enhances myofilament sen sitivity to Ca 2+ The suggestion that receptor mediated, GTP-binding protein-coupled activa tion of protein kinase C increases the Ca 2+ sen sitivity of contractile elements was also reported by some investigators (16,23,26). Furthermore, Karaki (27) mentioned that the contractility of vascular smooth muscle induced by receptor stimulants might be regulated not only by the increase in [Ca 2+]; but also by the increase of the Ca 2+ sensitivity of the contractile elements.…”

Section: Discussionmentioning

confidence: 86%

Propylbenzilylcholine Mustard(PrBCM)-Sensitive Cholinoceptors and Contractile Response to Partial Agonist in Guinea Pig Ileal Muscle.

et al. 1991

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Pilocarpine, a partial agonist, activates propylbenzilylcholine mustard (PrBCM)-sensitive cholinoceptors in the guinea pig ileal longitudinal muscle, while carbachol, a full agonist, predominantly activates PrBCM-resistant ones. Carbachol behaves as a partial agonist in the preparation treated with phenoxybenzamine and mainly activates PrBCM-sensitive cholinoceptors, as phenoxybenzamine preferably blocks PrBCM-resistant ones. The receptor occupancy-response curve for carbachol became a rectangular hyperbola, while pilocarpine showed a linear relation. After occlusion of cholinoceptors with phenoxybenzamine, carbachol showed a linear recep tor occupancy-response relation, suggesting that its contraction mechanisms after occlusion of cholinoceptors resemble those for pilocarpine. Both the agonists induced an increase in cytosolic Ca 2+ concentration ([Ca2+];) and tension development in a concentration-dependent manner under the conditions used herein. The slopes of the regression lines between [Ca 2+]; and tension development for pilocarpine in the untreat ed preparation and for carbachol in the preparation treated with phenoxybenzamine were significantly steeper than that for carbachol in the untreated preparation, sug gesting that carbachol in the phenoxybenzamine-treated preparation and pilocarpine induced a greater tension for a given increase in low [Ca 2+1i than did carbachol. Thus an activation of PrBCM-sensitive cholinoceptors might enhance the Ca2+-sensitivity of the contractile elements.

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Section: Discussionmentioning

confidence: 86%

Propylbenzilylcholine Mustard(PrBCM)-Sensitive Cholinoceptors and Contractile Response to Partial Agonist in Guinea Pig Ileal Muscle.

et al. 1991

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“…In permeabilized arterial muscles, it has also been reported that receptor agonists such as phenylephrine, noradrenaline and endothelin-l enhance Ca2"-induced contraction in the presence of GTP (Kitazawa et al, 1989;Nishimura et al, 1989;Anabuki et al, 1990;Hori et al, 1992). These receptor agonists induced contraction in the presence of the Ca2" channel blocker, verapamil, or in the absence of external Ca2" (with EGTA), and these contractions were not accompanied by an increase in MLC phosphorylation .…”

Section: Discussionmentioning

confidence: 99%

“…Activators of protein kinase C, phorbol esters, also induce contraction and increase Ca2+ sensitivity in intact and permeabilized smooth muscle preparations (Nishimura & van Breemen, 1989;Anabuki et al, 1990;Singer 1990;. Since various receptor agonists activate inositol phosphate metabolism to generate the endogenous activator of protein kinase C, diacylglycerol (Berridge, 1984;Nishizuka 1984), it is possible that activation of protein kinase C is…”

Section: Introductionmentioning

confidence: 99%

Different pathways of calcium sensitization activated by receptor agonists and phorbol esters in vascular smooth muscle

Hori¹,

Sato

Miyamoto

et al. 1993

British J Pharmacology

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1 It has been shown that receptor agonists and activators of protein kinase C, phorbol esters, increase Ca2+ sensitivity of contractile elements in vascular smooth muscle. To discover if protein kinase C is involved in the agonist-mediated Ca2" sensitization, we examined the effects of receptor agonists in the rat isolated aorta in which protein kinase C activity had been diminished by pretreatment with phorbol 12-myristate 13-acetate for 24 h.2 In the aorta with protein kinase C activity, a high concentration (1 gM) of 12-deoxyphorbol 13-isobutyrate induced contraction and a low concentration (100 nM) potentiated high K+-induced contraction. In addition, prostaglandin F2. induced greater contractions than high K+ at a given cytosolic Ca2+ level. The maximally effective concentrations of noradrenaline and endothelin-1 also induced greater contraction than high K+. In the aorta without protein kinase C activity, the contraction induced by 12-deoxyphorbol 13-isobutyrate and its potentiation of the high K+-induced contraction were abolished. However, prostaglandin F2.., noradrenaline and endothelin-1 still induced a greater contraction than high K+.3 In the aorta without protein kinase C activity, noradrenaline, endothelin-l and prostaglandin F2,, but not 12-deoxyphorbol 13-isobutyrate, induced contractions in the presence of the Ca2+ channel blocker, verapamil, or in the absence of external Ca2+, by increasing Ca2+ sensitivify. 4 In the permeabilized preparations, inhibition of protein kinase C activity abolished the effect of potentiation of the Ca2'-induced contraction by 12-deoxyphorbol 13-isobutyrate although the potentiation of the contraction by prostaglandin F2C did not change.5 These results suggest that there are two pathways for Ca21 sensitization in rat aorta; a protein kinase C-dependent pathway which is activated by phorbol esters, and a protein kinase C-independent pathway which is activated by receptor agonists.

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“…These results suggest that NA enhances Ca2+-induced contraction through an activation of G-protein-mediated pathways. It was recently reported that in oc-toxintreated skinned smooth muscle strips of the rabbit mesenteric artery, a high concentration of pinacidil (100 ,tM) inhibited Ca2+-induced contraction in the presence but not in the absence of NA (Anabuki, Hori, Ozaki, Kato & Karaki, 1990). In ,-escin-treated skinned smooth muscle of the rabbit mesenteric artery, although pinacidil (10 /LM) inhibited the Ca2+-induced contraction in the presence or absence of NA (Itoh, Suzuki & Kuriyama, 1991), pinacidil (> 3 ,SM) inhibited Ca2+-induced contraction more in the presence of NA with GTP than in the absence of NA and GTP.…”

Section: Introductionmentioning

confidence: 99%

Membrane hyperpolarization inhibits agonist‐induced synthesis of inositol 1,4,5‐trisphosphate in rabbit mesenteric artery.

Itoh

Seki

Suzuki

et al. 1992

The Journal of Physiology

187

165

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Mechanisms of pinacidil-induced vasodilatation

Cited by 30 publications

References 27 publications

Propylbenzilylcholine Mustard(PrBCM)-Sensitive Cholinoceptors and Contractile Response to Partial Agonist in Guinea Pig Ileal Muscle.

Propylbenzilylcholine Mustard(PrBCM)-Sensitive Cholinoceptors and Contractile Response to Partial Agonist in Guinea Pig Ileal Muscle.

Different pathways of calcium sensitization activated by receptor agonists and phorbol esters in vascular smooth muscle

Membrane hyperpolarization inhibits agonist‐induced synthesis of inositol 1,4,5‐trisphosphate in rabbit mesenteric artery.

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