Blockade of neuropeptide Y-induced potentiation of noradrenaline-evoked vasoconstriction by D-myo-inositol-1.2.6-trisphosphate (PP56) in rabbit femoral arteries

Adamsson, M.; Edvinsson, Lars

doi:10.1016/0143-4179(91)90068-t

Cited by 21 publications

(8 citation statements)

References 10 publications

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“…In the rabbit femoral artery acute removal of extracellular calcium has little effect on the neuropeptide Y evoked potentiation whereas prolonged exposure to a calcium-free medium containing EGTA abolished the potentiating effect of neuropeptide Y These results suggest that intracellular calcium pools have a more important role, the potentiation possibly reflecting enhanced mobilization of an intracellularly sequestered calcium pool (Fallgren et al 1993). The potentiating effect of neuropeptide Y is blocked by u-trinositol in low concentrations (1.0-10 nM) (Adamsson & Edvinsson 1991;.…”

Section: Inosilol Derivntives Nsfunctiona1 Neuropeptide Y Inhibitorsmentioning

confidence: 85%

“…The inositol derivative a-trinositol ( fig. 2) is a neuropeptide Y inhibitor (Edvinsson et al 1990; Adamsson & Edvinsson 1991 ; Adamsson et a/. 1992).…”

Section: Inosilol Derivntives Nsfunctiona1 Neuropeptide Y Inhibitorsmentioning

confidence: 99%

“…Furthermore, it was observed that the potentiating effect of neuropeptide Y on noradrenaline-induced vasoconstriction in rabbit and guinea pig arteries was inhibited by a-trinositol at nM concentrations ( fig. 3B) (Adamsson & Edvinsson 1991;Adamsson et crl. 1992).…”

Section: Inosilol Derivntives Nsfunctiona1 Neuropeptide Y Inhibitorsmentioning

confidence: 99%

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Neuropeptide Y in sympathetic co-transmission—Recent advances in the search for neuropeptide Y antagonists

Edvinsson¹,

Erlinge²

1994

Neuropeptides

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Section: Inosilol Derivntives Nsfunctiona1 Neuropeptide Y Inhibitorsmentioning

confidence: 85%

“…The inositol derivative a-trinositol ( fig. 2) is a neuropeptide Y inhibitor (Edvinsson et al 1990; Adamsson & Edvinsson 1991 ; Adamsson et a/. 1992).…”

Section: Inosilol Derivntives Nsfunctiona1 Neuropeptide Y Inhibitorsmentioning

confidence: 99%

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Neuropeptide Y in sympathetic co-transmission—Recent advances in the search for neuropeptide Y antagonists

Edvinsson¹,

Erlinge²

1994

Neuropeptides

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“…There is increasing evidence that D-myo-inositol-1,2,6-triphosphate (a-trinositol, previously known as PP56) has unusual pharmacological attributes. For example, x-trinositol appears to act as an antagonist of the effects of exogenous neuropeptide Y (NPY), both in vivo and in vitro (Edvinsson et al, 1990;Adamsson & Edvinsson, 1991;Sun et al, 1991a,b;Potter et al, 1992;Donoso et al, 1993;Schweiler & Hjemdahl, 1993), although this finding is not unanimous (Pernow et al, 1992;Feth et al, 1993). However, in the study of Pernow et al (1992) only a single bolus injection of a-trinositol was given and Feth et al (1993) performed only few experiments.…”

Section: Introductionmentioning

confidence: 99%

Effects of chronic infusions of α‐trinositol on regional and cardiac haemodynamics in conscious rats

Gardiner

Kemp

Fallgren

et al. 1994

British J Pharmacology

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1 Male, Long Evans rats (350-450 g) were chronically instrumented for the measurement of renal, mesenteric and hindquarters haemodynamics, and were given three consecutive, 24 h infusions of vehicle (sterile saline at 0.3 ml h-'; n = 8) or a-trinositol (D-myo-inositol-1,2,6-triphosphate) at 5, 20 and 80mg kg' h-' (0.3 ml h'; n = 9). During infusion of a-trinositol at 5 or 20mg kg-Ih-', cardiovascular changes were little different from those seen during saline infusion. However, during infusion of a-trinositol at 80 mg kg-' h-' there were increases in hindquarters vascular conductance, renal flow and vascular conductance, that were all significantly different from the changes seen in the saline group. Infusion of a-trinositol at the high dose in naive rats (n = 8) had even more marked vasodilator effects. 2 Two groups of rats (n = 8 in each), chronically instrumented for the measurement of cardiac haemodynamics, were given 48 h infusions of saline (0.3 ml h-1) or a-trinositol (2 mg kg-' bolus, 80 mg kg' h-' infusion at 0.3 ml h-'). During the infusion of saline, there were slight reductions in heart rate, cardiac index, peak aortic flow, dF/dtmax and central venous pressure. In the animals receiving a-trinositol, with the exception of central venous pressure, all the above variables, together with total peripheral conductance, increased. 3 These results, collectively, indicate that incremental infusions of a-trinositol do not reveal its full vasodilator potential, possibly due to concurrent activation of counter-regulatory vasoconstrictor mechanisms. However, infusion of a-trinositol at a high dose causes substantial increases in renal, mesenteric and hindquarters flows and vascular conductances, supported by significant increases in indices of cardiac inotropism. Such effects, in the absence of significant hypotension, tachycardia or signs of desensitization, give a-trinositol a unique cardiovascular profile.

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“…However, relatively little is known of the pharmacology of inositol phosphates, although a-trinositol (D-myoinositol-1,2,6 triphosphate; previously known as PP56) has been shown to act as a functional antagonist of the cardiovascular actions of exogenous neuropeptide Y (NPY) and ATP, in vitro and in vivo (Adamsson & Edvinsson, 1991;Sun et al, 1991ab;Wahlestedt et al, 1992;Schweiler & Hjemdahl, 1993). Furthermore, a-trinositol has been found to exert anti-inflammatory, anti-aggregatory and anti-neuropathic actions in various animals models (Claxson et al, 1990; 1Author for correspondence.…”

Section: Introductionmentioning

confidence: 99%

Effects of glibenclamide on the regional haemodynamic actions of α‐trinositol and its influence on responses to vasodilators in conscious rats

Gardiner

Kemp

March

et al. 1996

British J Pharmacology

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1 In conscious rats, a-trinositol (D-myo-inositol-1, 2, 6 triphosphate; 5-80 mg kg-' h-' infusion) caused dose-dependent hypotension, tachycardia and hyperaemic dilatation in renal, mesenteric and hindquarters vascular beds. These effects were accompanied by inhibition of the renal vasodilator effects of acetylcholine (ACh), and of the mesenteric vasodilator effects of sodium nitroprusside (SNP) and, particularly, of levcromakalim (LCK).2 In the light of the latter finding, in a second experiment, we assessed the influence of the KATP channel inhibitor, glibenclamide (20 mg kg-'), on resting haemodynamics, on responses to ACh, bradykinin (BK), SNP and LCK, on the haemodynamic action of a-trinositol, and on the effects of the latter on responses to the vasodilators, over a period of 3 days. 3 In the presence of saline, glibenclamide caused a reproducible pressor effect, accompanied by renal, mesenteric, and hindquarters vasoconstrictions on all 3 experimental days; these effects were unrelated to changes in blood glucose. In the presence of glibenclamide, only the hindquarters vasodilator response to BK, and all the cardiovascular actions of LCK were inhibited. 4 On the first experimental day, the hindquarters vasodilator effect of cx-trinositol was substantially inhibited by glibenclamide, the renal vasodilatation less so, and the mesenteric vasodilatation not at all. However, over the subsequent two days, the mesenteric vasodilator effect of ac-trinositol became increasingly sensitive to glibenclamide. 5 In the presence of a-trinositol and glibenclamide, on the first experimental day, the inhibition of the renal vasodilator effect of ACh was no greater than with a-trinositol alone in the first experiment. Moreover, on the third experimental day, both before and after glibenclamide, the inhibition by atrinositol of the renal vasodilator response to ACh was less than on the first experimental day. Similarly, the a-trinositol-induced inhibition of the mesenteric vasodilator effect of SNP, and of the hindquarters vasodilator action of BK, waned over the 3 experimental days. The inhibition of the cardiovascular effects of LCK were similar on all 3 experimental days, but no greater in the presence of ax-trinositol and glibenclamide than with glibenclamide alone.6 These results indicate that KATP channels are involved in the maintenance of resting vasodilator tone in renal, mesenteric and hindquarters vascular beds. However, although additional activation of KATP channels is responsible for all the haemodynamic effects of LCK, it contributes only to the hindquarters vasodilator action of BK and is not involved in any of the responses to ACh or SNP. The hindquarters, renal and mesenteric vasodilator effects of a-trinositol may involve (in the same rank order) activation of KATP channels, probably through an indirect mechanism. However, it is unlikely that direct or indirect interaction of a-trinositol with KATP channels explains the ability of the drug to inhibit the renal vasodilator action of ACh, or the mesenteric v...

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Blockade of neuropeptide Y-induced potentiation of noradrenaline-evoked vasoconstriction by D-myo-inositol-1.2.6-trisphosphate (PP56) in rabbit femoral arteries

Cited by 21 publications

References 10 publications

Neuropeptide Y in sympathetic co-transmission—Recent advances in the search for neuropeptide Y antagonists

Neuropeptide Y in sympathetic co-transmission—Recent advances in the search for neuropeptide Y antagonists

Effects of chronic infusions of α‐trinositol on regional and cardiac haemodynamics in conscious rats

Effects of glibenclamide on the regional haemodynamic actions of α‐trinositol and its influence on responses to vasodilators in conscious rats

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