Agonist concentration-dependent differential responsivity of a human platelet purinergic receptor: pharmacological and kinetic studies of aggregation, deaggregation and shape change responses mediated by the purinergic P2Y1 receptor in vitro.

Platelet shape change (SC), aggregation and deaggregation responses are integral components of hemostasis that are elicited and modulated in vivo by the simultaneous activation of several membrane receptors. Selective activation of the purinergic P2Y1 receptor in vivo elicits a sustained SC and a small, transient aggregation response that is reversed rapidly by a robust deaggregation response (Platelets 2003; 14: 89). Using a kinetics-based turbidimetric approach to study the modulation of these concurrent components of human platelet responses, we demonstrate that these P2Y1 receptor-related responses and a number of their kinetic and steady-state characteristics are differentially elicited and modulated.

Diversity of signaling underlying responses mediated by selective activation of the platelet thromboxane A2 (TXA2) receptor; pharmacological and kinetic studies in vitro.

Selective activation of the platelet TXA2 receptor is sufficient to mediate concurrent aggregation, deaggregation and shape change (SC) responses without activation of known Gi-coupled receptors (Platelets 2003; 14: 89). However, Gi-coupled receptor activation strongly influences the hemostasis response in vivo. This study investigated the modulatory effects of two signaling pathways related to Gi-coupled receptor activation, stimulation of phosphoinositide 3-kinases (PI3Ks) and inhibition of adenylyl cyclase (AC), on the aggregation, deaggregation and SC components of the platelet activation response.

Atenolol may not modify anesthetic depth indicators in elderly patients--a second look at the data.

Purpose: Decreased cardiac chronotropic response in elderly patients along with concomitant ss-blockade may suppress the autonomic responsiveness to surgical stimulation and subsequently obscure episodes of "light anesthesia".

Methods: We analyzed post hoc computerized data from our previous study evaluating the effects of perioperative atenolol administration. Bispectral index (BIS) and the performance of routine anesthetic depth indicators were analyzed in 45 patients undergoing abdominal surgery: Group I (n = 12), isoflurane/fentanyl/nitrous oxide in oxygen anesthesia; Group II (n = 16), isoflurane/fentanyl/nitrous oxide in oxygen with 10 mg atenolol intravenously prior to anesthesia; Group III (n = 17), isoflurane/fentanyl/nitrous oxide in oxygen with a maximum end-tidal isoflurane concentration of 0.

Interleukin balance and early recovery from anesthesia in elderly surgical patients exposed to beta-adrenergic antagonism.

Study Objective: To determine whether proinflammatory and antiinflammatory cytokines, as measured in blood specimens, would correlate with improved SF-36 physical composite scores observed in elderly surgical patients who were administered perioperative atenolol.

Design: Post hoc analysis of data from a randomized clinical study.

Setting: Department of Anesthesiology, Mount Sinai Medical School, New York.

Concurrent responses elicited by isolated activation of platelet Gq-coupled receptors, in vitro: a novel approach for their separation and analysis.

This study tested the hypothesis that aggregation mediated by activation of a single G(q)-coupled receptor can be studied quantitatively if four concurrent but distinct components of the observed platelet response, autocrine stimulation, shape change (SC), aggregation and deaggregation, are separately measured. Responses mediated by two G(q)-coupled receptors, the TXA(2) and the P2Y(1), were assayed by a novel, kinetics-based turbidimetric approach. Blocking the autocrine stimulation with a cocktail of receptor antagonists revealed rapid and sustained SC that largely masked the aggregation.