Abstract. ATP and hydrolysis products of ATP like adenosine regulate the chemotaxis of neutrophils by activating purinoceptors and adenosine receptors. The present study was designed to examine exogenous ATP, activation of purinoceptors, and activation of A 3 adenosine receptor as key steps in the signal cascades that control cell orientation and migration of rat neutrophils. One or more of those steps might be potential therapeutic targets for treatment of inflammatory diseases. The chemotaxis of rat neutrophils was stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) and measured with an EZ-TAXIScan apparatus. The effects of apyrase, exogenous ATP, suramin (P2X and P2Y blocker), PPADS (a P2X blocker), TNP-ATP (P2X 1 and P2X 3 antagonist), and Reactive Blue 2 (a P2Y blocker) on the chemotactic response were also investigated. Rat neutrophil chemotaxis was significantly suppressed by apyrase. fMLP induced rat neutrophil chemotaxis was potentiated by ATP, blocked by suramin, not affected by PPADS or TNP-ATP, and significantly inhibited by RB-2. Western blotting showed that A 3 , P2Y 2 , and P2Y 11 were expressed in rat neutrophils. The chemotactic response of rat neutrophils to fMLP stimulation is potentiated by ATP via P2Y 11 purinoceptors but not P2X purinoceptors or A 3 adenosine receptor, and that the response plays a critical role in host defense and pathogenicity.[Supplementary Movies: available only at http://dx
Background and purpose:The chicken anterior mesenteric artery contains an outer longitudinal smooth muscle layer, whose neural regulation remains to be elucidated. ATP evokes a depolarization in the smooth muscle through P2Y purinoceptors. However, there may be an additional inhibitory regulation because blockade of P2Y purinoceptors converts the depolarization to hyperpolarization. The objective of the present study was to examine the mechanism underlying this hyperpolarization. Experimental approach: Membrane potentials of longitudinal smooth muscle of the chicken mesenteric artery were recorded with a microelectrode technique. Perivascular nerves were stimulated by applying electrical field stimulation (EFS). Key results: EFS induced a hyperpolarization in preparations obtained from 5-week-old chickens, whereas it evoked a depolarization in those from 12-week-old chickens. The EFS-evoked hyperpolarization in 5-week-old chickens was blocked by a non-specific purinoceptor antagonist, suramin, and by a specific P2X purinoceptor antagonist, pyridoxal phosphate-6-azophenyl-2′,4′-disulphonic acid. Desensitization of the P2X purinoceptor with its agonist a,b-MeATP significantly suppressed EFS-evoked hyperpolarization. Blockade of the P2Y purinoceptor did not affect EFS-evoked hyperpolarization. The application of the NOS inhibitor Nw-nitro-L-arginine methyl ester or the removal of the endothelium inhibited the hyperpolarization. The application of the nitric oxide (NO) donor sodium nitroprusside mimicked the hyperpolarization. Reverse transcriptase-PCR showed that P2X purinoceptors are expressed in the endothelium of the anterior mesenteric artery. Conclusions and implications: Hyperpolarization in the longitudinal smooth muscle of the chicken anterior mesenteric artery was induced by ATP. ATP released from perivascular nerves may act on P2X purinoceptors in the endothelium and thereby stimulate NO production.
Brown adipose tissue (BAT) is a heat-producing organ that plays an important role in maintenance of energy homeostasis. The purpose of this study was to test a novel method for stimulating BAT thermogenesis in rats. Application of electrical field stimulation to the dorsal surface of interscapular BAT caused a substantial rise in tissue temperature without affecting rectal temperature. The electrical stimulation failed to raise BAT temperature on the 2nd day after surgical sympathetic denervation. This is unlikely to be due to loss of thermogenic capacity, since neither UCP1 contents nor norepinephrine-induced thermogenesis were diminished 2 days after the denervation. A pharmacological experiment revealed that the BAT thermogenesis induced after electrical stimulation is mediated through β-adrenoceptors. The present study demonstrates that electrical stimulation applied to the dorsal surface of BAT is able to activate thermogenesis of BAT through mediation of norepinephrine released from sympathetic nerves. Our findings may provide a basis for developing a novel therapeutic procedure for obesity and related disorders.Brown adipose tissue (BAT) is a heat-producing organ that plays an important role in recovery from hibernation or hypothermia and in maintenance of body temperature in newborns and cold-exposed mammals (3,9,15). BAT is also important for maintaining energy balance during spontaneous hyperphagia, as it is activated in response to diet (11). It has been widely believed that BAT contributes little, if anything, to the maintenance of energy homeostasis in adult humans. However, recent studies have revealed that BAT is active not only in newborns but also in adults (4,13,19,20). The fact that BAT thermogenesis in adult humans can be acutely activated by cold stimulus (7, 13) offered a novel therapeutic strategy to reduce body weight and to prevent weight gain. BAT thermogenesis is activated by sympathetic nerves that richly innervate the tissue (2, 3, 9). Cellular events associated with heat production involve binding of norepinephrine (NE) released from sympathetic nerve endings to β-adrenergic receptors, increased breakdown of triglycerides into fatty acids, and increase in mitochondrial oxidation. The presence of uncoupling protein 1 (UCP1) in BAT allows a short-circuit of the proton gradient across the inner mitochondrial membrane, thus uncoupling fuel oxidation with ATP synthesis (9). It is reasonable to expect that increases in BAT mass and UCP1 expression are effective as a therapeutic approach for obesity. However, the increased thermogenic capacity of BAT is not directly linked with enhancement of basal metabolic rate. Indeed, hyperplastic BAT that has developed in rodents adapted to the cold becomes functionally inactive immediately after
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.