Antivasoconstrictor and Antiaggregatory Activities of Picotamide Unrelated to Thromboxane A2 Antagonism

1997 ◽  
Vol 78 (05) ◽  
pp. 1385-1391 ◽  
Author(s):  
Roberta Vezza ◽  
Domenico Spina ◽  
Ronald J Tallarida ◽  
Malevika Nathan ◽  
Clive P Page ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Shape Change ◽  
Thromboxane A2 ◽  
Inhibitory Effects ◽  
Experimental Conditions ◽  
Vasoactive Substances ◽  
Vasoconstrictor Effect ◽  
Synthase Inhibitor

SummaryPicotamide is a dual thromboxane (Tx) A2 receptor antagonist/Tx synthase inhibitor although some observations suggest an anti-vasoconstrictor effect independent of TxA2 inhibition/antagonism. The aim of our study was to assess whether picotamide antagonises vascular contractions induced by different vasoactive substances in vitro. Picotamide inhibited competitively the contraction of rabbit aortic rings induced by the TxA2 mimetic U46619 (pA2 = 3.59) but also the contractions induced by phenylephrine (pA2 = 3.93) and serotonin (5-HT) (pA2 = 5.81) although in a not competitive way. Picotamide did not inhibit potassium-induced contractions, thus excluding aspecific effects on vascular smooth muscle. Picotamide inhibited 5-HT-induced platelet aggregation in vitro with an IC50 (212 μM) similar to that found when other aggregating stimuli are used, but it did not affect shape change (IC50> 1 mM) suggesting that the effects of picotamide can not be ascribed to 5-HT2-receptor antagonism; in the same experimental conditions neither a Tx-receptor antagonist (BM13.177) nor a dual Tx-receptor antagonist/synthase inhibitor (ridogrel) affected 5-HT-induced platelet responses.Our studies demonstrate that picotamide exerts antivasoconstrictor and platelet inhibitory effects unrelated to TxA2 antagonism. This activity may contribute to the anti-thrombotic/anti-ischaemic effects of the drug in vivo.

Interaction between prolactin and catecholamines on hypothalamic GnRH release in vitro

1996 ◽  
Vol 151 (2) ◽  
pp. 269-275 ◽  
Author(s):  
A E Calogero ◽  
N Burrello ◽  
A M Ossino ◽  
R F A Weber ◽  
R D'Agata
Keyword(s):  
Receptor Antagonist ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Experimental Conditions ◽  
Adrenergic Mechanism ◽  
Gnrh Release ◽  
Β Adrenergic Receptors

Abstract Brain catecholamines have been implicated in the regulation of gonadotrophin release. It has been recently reported that noradrenaline (NA), applied within the hypothalamic paraventricular nucleus, suppresses the pulsatile release of LH in the rat through a corticotrophin-releasing hormone (CRH)-dependent mechanism. Prolactin (PRL) is also able to suppress hypothalamic GnRH release following activation of the CRH-releasing neurone. Given that PRL stimulates the release of NA from hypothalamic explants and that NA stimulates the release of hypothalamic CRH, we hypothesized that this neurotransmitter may be involved in the intrahypothalamic neuroendocrine circuit mediating the inhibitory effects of PRL on GnRH release. To test this hypothesis, we evaluated the effects of PRL on GnRH release in the presence of α- or β-adrenergic receptor antagonists using a static hypothalamic organ culture system which enabled us to evaluate immunoreactive GnRH (iGnRH) release from individually incubated, longitudinally halved hypothalami. As previously shown, PRL at a concentration of 100 nm inhibited basal iGnRH release by about 35%. Phentolamine, a non-selective α-adrenergic receptor antagonist, prazosin, an α1-receptor antagonist, and yohimbine, an α2-receptor antagonist, overcame the inhibitory effect of PRL on iGnRH release in a concentration-dependent fashion. In contrast, propranolol, a non-selective β-adrenergic receptor antagonist, atenolol, a β1-receptor antagonist, and ICI-118,551, a β2-receptor antagonist, had no effect. None of these compounds had any effect on basal iGnRH release. These findings suggested that an α-adrenergic mechanism is involved in the suppressive effects of PRL on GnRH release. Since the activation of α-adrenergic receptors increases hypothalamic CRH release, we evaluated whether PRL stimulates CRH release via an α-adrenergic mechanism. PRL stimulated basal CRH release by about twofold and this effect was inhibited by phentolamine in a concentration-dependent fashion. In conclusion, α-, but not β-, adrenergic receptors mediate the inhibitory effects of PRL on GnRH release in vitro. We speculate that, at least under these experimental conditions, PRL inhibits GnRH release through an α-adrenergic mechanism which activates the CRH-secreting neurone. Journal of Endocrinology (1996) 151, 269–275

Tetrahydrocurcumin Downregulates MAPKs/cPLA2 Signaling and Attenuates Platelet Thromboxane A2 Generation, Granule Secretion, and Thrombus Growth

2021 ◽  
Author(s):  
Weiqi Li ◽  
Yongjie Ma ◽  
Chunmei Zhang ◽  
Binlin Chen ◽  
Xiandan Zhang ◽  
...  
Keyword(s):  
Thrombus Formation ◽  
Biological Activities ◽  
Thromboxane A2 ◽  
Mapk Signaling ◽  
Inhibitory Effects ◽  
Platelet Factor ◽  
Thrombosis Model ◽  
Granule Secretion

AbstractPlatelet granule secretion plays a key role in atherothrombosis. Curcumin, a natural polyphenol compound derived from turmeric, exerts multiple biological activities. The current study sought to investigate the efficacy of tetrahydrocurcumin (THC, the major active metabolite of curcumin) on platelet granule secretion in vitro and thrombus formation in vivo. We found that THC significantly attenuated agonist-induced granule secretion in human gel-filtered platelets in vitro, including CD62P and CD63 expression and platelet factor 4, CCL5, and adenosine triphosphate release. These inhibitory effects of THC were partially mediated by the attenuation of cytosolic phospholipase A2 (cPLA2) phosphorylation, leading to a decrease in thromboxane A2 (TxA2) generation. Moreover, the MAPK (Erk1/2, JNK1/2, and p38 MAPK) signaling pathways were downregulated by THC treatment, resulting in reduced cPLA2 activation, TxA2 generation, and granule secretion. Additionally, THC and curcumin attenuated murine thrombus growth in a FeCl3-induced mesenteric arteriole thrombosis model in C57BL/6J mice without prolonging the tail bleeding time. THC exerted more potent inhibitory effects on thrombosis formation than curcumin. Through blocking cyclooxygenase-1 activity and thus inhibiting platelet TxA2 synthesis and granule secretion with aspirin, we found that THC did not further decrease the inhibitory effects of aspirin on thrombosis formation. Thus, through inhibiting MAPKs/cPLA2 signaling, and attenuating platelet TxA2 generation, granule secretion, and thrombus formation, THC may be a potent cardioprotective agent.

scholarly journals Intrinsic activity of the non-prostanoid thromboxane A2 receptor antagonist, daltroban (BM 13,505), in human platelets in vitro and in the rat vasculature in vivo

1995 ◽  
Vol 115 (1) ◽  
pp. 210-216 ◽  
Author(s):  
Frédéric Bertolino ◽  
Jean-Pierre Valentin ◽  
Myriam Maffre ◽  
Françoise Grelac ◽  
Anne-Marie Bessac ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Thromboxane A2 ◽  
Human Platelets ◽  
Intrinsic Activity ◽  
Thromboxane A2 Receptor

scholarly journals ZD1542, a potent thromboxane A2 synthase inhibitor and receptor antagonist in vitro

1993 ◽  
Vol 110 (4) ◽  
pp. 1600-1606 ◽  
Author(s):  
R.P. Brownlie ◽  
N.J. Brownrigg ◽  
H.M. Butcher ◽  
R. Garcia ◽  
R. Jessup ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Thromboxane A2 ◽  
Synthase Inhibitor

scholarly journals Effects of altered tonicity by sodium chloride onl-tryptophan binding to hepatic nuclei

2000 ◽  
Vol 278 (6) ◽  
pp. C1237-C1245 ◽  
Author(s):  
Herschel Sidransky ◽  
Ethel Verney ◽  
Jan Orenstein
Keyword(s):  
Kinetic Studies ◽  
Significant Inhibition ◽  
Inhibitory Effects ◽  
Experimental Conditions ◽  
Isolated Nuclei ◽  
Hepatic Cells ◽  
In Vitro Incubation ◽  
Nacl Concentration

This study was concerned with the effects of NaCl administered in vivo or added in vitro to isolated nuclei on [3H]tryptophan binding to rat hepatic nuclei assayed in vitro. Hypertonic (10.7%) NaCl administered in vivo to rats caused at 10 min a marked decrease in in vitro binding (total and specific) of [3H]tryptophan to hepatic nuclei. In vitro incubation of isolated hepatic nuclei, but not of isolated nuclear envelopes, with added NaCl (particularly at 0.125 × 10−4 M and 0.25 × 10−4 M) revealed significant inhibition of [3H]tryptophan binding. However, isolated hepatic nuclear envelopes prepared after in vitro incubation of isolated nuclei with added NaCl did show inhibition of [3H]tryptophan binding (total and specific) compared with controls. Other salts (KCl, MgCl2, NaHCO3, NaC2H3O2, NaF, or Na2SO4), at similar concentrations to that of NaCl except for MgCl2, when added to isolated nuclei did not appreciably inhibit nuclear tryptophan binding. Kinetic studies of in vitro nuclear [3H]tryptophan binding in the presence of 0.125 × 10−4 M NaCl revealed that binding decreased at 0.5 h and continued to 2 h compared with nuclear [3H]tryptophan binding with controls (without NaCl addition). The results obtained in vivo in rats and those obtained in vitro with isolated hepatic nuclei revealed NaCl-induced inhibitory effects on [3H]tryptophan binding to hepatic nuclei. Although the inhibitory effects were similar under the two different experimental conditions, the mechanism for each may be different in that the NaCl concentration in hepatic cells after administration of NaCl in vivo was appreciably higher than the low levels added in vitro to the isolated hepatic nuclei.

Inhibitory effects of epimedium herb water extract on the inflammatory response in vitro and in vivo

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381
Author(s):  
YC Oh ◽  
YH Jeong ◽  
WK Cho ◽  
SJ Lee ◽  
JY Ma
Keyword(s):  
Inflammatory Response ◽  
Water Extract ◽  
Inhibitory Effects

The Effects of Brinolase (Fibrinolytic Enzyme from Aspergillus Oryzae) on Platelet Aggregation of Dog and Man

1972 ◽  
Vol 28 (01) ◽  
pp. 031-048 ◽  
Author(s):  
W. H. E Roschlau ◽  
R Gage
Keyword(s):  
Platelet Aggregation ◽  
Aspergillus Oryzae ◽  
Degradation Products ◽  
Blood Platelet ◽  
Human Platelets ◽  
Fibrinolytic Enzyme ◽  
Inhibitory Effects ◽  
Blood Platelet Aggregation

SummaryInhibition of blood platelet aggregation by brinolase (fibrinolytic enzyme from Aspergillus oryzae) has been demonstrated with human platelets in vitro and with dog platelets in vivo and in vitro, using both ADP and collagen as aggregating stimuli. It is suggested that the optimal inhibitory effects of brinolase occur indirectly through the generation of plasma fibrinogen degradation products, without compromising platelet viability, rather than by direct proteolysis of platelet structures.

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