Identification and characterization of platelet α2-adrenoceptors and imidazoline receptors in rats, rabbits, cats, dogs, cattle, and horses

Tsai

BioMed Research International

et al. 2014

The agonists of imidazoline I-1 receptors (I-1R) are widely used to lower blood pressure. It has been indicated that guanidinium derivatives show an ability to activate imidazoline receptors. Also, allantoin has a chemical stricture similar to guanidinium derivatives. Thus, it is of special interest to characterize the effect of allantoin on I-1R. In conscious male spontaneous hypertensive rats (SHRs), mean blood pressure (MBP) was recorded using the tail-cuff method. Furthermore, the hemodynamic analyses in catheterized rats were applied to measure the actions of allantoin in vivo. Allantoin decreased blood pressures in SHRs at 30 minutes, as the most effective time. Also, this antihypertensive action was shown in a dose-dependent manner from SHRs treated with allantoin. Moreover, in anesthetized rats, allantoin inhibited cardiac contractility and heart rate as showing in hemodynamic dP/dt max significantly. Also, the peripheral blood flow was markedly increased by allantoin. Both actions were diminished by efaroxan at the dose sufficient to block I-1R. Thus, we suggest that allantoin, as I-1R agonist, has the potential to develop as a new therapeutic agent for hypertension in the future.

Section: Discussionmentioning

confidence: 99%

“…These agents were introduced to reduce blood pressure mainly through an activation of specific receptors in RVLM [23, 24]. It has been documented that I1- IR agonist(s) may provide more useful therapy of hypertension than clonidine due to the low incidence of the side effect(s) including sedation [25].…”

Section: Discussionmentioning

confidence: 99%

Antihypertensive Action of Allantoin in Animals

Tsai

BioMed Research International

et al. 2014

“…It was and still is widely used in various experimental studies in vitro [10, 19, 34] and in vivo in conscious animals [3, 5, 7] and as an antagonist of general anesthesia [11, 22, 24, 48]. …”

Section: Introductionmentioning

confidence: 99%

Yohimbine is a 5-HT1A agonist in rats in doses exceeding 1mg/kg.

Zaretsky

Zaretskaia

DiMicco

et al. 2015

Neuroscience Letters

Yohimbine is a prototypical alpha2-adrenergic receptor antagonist. Due to its relatively high selectivity, yohimbine is often used in experiments whose purpose is to examine the role of these receptors. For example, yohimbine has been employed at doses of 1–5 mg/kg to reinstate drug-seeking behavior after extinction or to antagonize general anesthesia, an effects presumably being a consequence of blocking alpha2-adrenergic receptors. In this report we characterized dose-dependent autonomic and behavioral effects of yohimbine and its interaction with an antagonist of 5-HT1A receptors, WAY 100635. In low doses (0.5 – 2 mg/kg i.p.) yohimbine induced locomotor activation which was accompanied by a tachycardia and mild hypertension. Increasing the dose to 3–4.5 mg/kg reversed the hypertension and locomotor activation and induced profound hypothermia. The hypothermia as well as the suppression of the locomotion and the hypertension could be reversed by the blockade of 5-HT1A receptors with WAY 100635. Our data confirm that yohimbine possesses 5-HT1A properties, and demonstrated that in doses above 1 mg/kg significantly activate these receptors.

Biochimica et Biophysica Acta (BBA) - Biomembranes

“…[6,10] However, there is still limited information on how non-OCS platelets maintain hemostasis comparable to platelets with an OCS, thus making it harder to pinpoint the function of the OCS. This study focuses on how the membrane of the platelets with (mouse and rabbit) and without (cow) an OCS changes to enable normal platelet function, including measurement of phospholipid and cholesterol content while accounting for platelet sizes before and after activation.…”

Section: Introductionmentioning

confidence: 99%

Platelet membrane variations and their effects on δ-granule secretion kinetics and aggregation spreading among different species

Gruba

Koseoglu

Meyer

et al. 2015

Background Platelet exocytosis is regulated partially by the granular/cellular membrane lipids and proteins. Some platelets contain a membrane-bound tube, called an open canalicular system (OCS), which assists in granular release events and increases the membrane surface area for greater spreading. The OCS is not found in all species, and variations in membrane composition can cause changes in platelet secretion. Since platelet studies use various animal models, it is important to understand how platelets differ in both their composition and granular release to draw conclusions among various models. Methods The relative phospholipid composition of the platelets with (mouse, rabbit) and without (cow) an OCS was quantified using UPLC-MS/MS. Cholesterol and protein composition was measured using an Amplex Red Assay and BCA Assay. TEM and dark field imaging were used to gather platelet images and analyzed with Image J. Granular release was monitored with single cell carbon fiber microelectrode amperometry. Results Cow platelets contained greater amounts of cholesterol and sphingomyelin. In addition, they yield greater serotonin release and longer δ granule secretion times. Finally, they showed greater spreading area with a greater range of spread. Conclusion Platelets containing an OCS had more similarities in their membrane composition and secretion kinetics compared to cow platelets. However, cow platelets showed greater fusion pore stability which could be due to extra sphingomyelin and cholesterol, the primary components of lipid rafts. In addition, their greater stability may lead to more granules assisting in spreading. General Significance Highlights fundamental membrane differences and their effects on platelet secretion