“…The first studies to suggest the presence of betaAR in the epidermis were functional ones that demonstrated an increase in levels of cAMP in keratinocytes after stimulation with non-specific betaAR agonists [8,9]. Subsequently, work using agonists and antagonists with specificity for the different adrenergic receptor subtypes demonstrated that the increase in keratinocyte…”
Section: Physiology Of the Beta2 Adrenergic Receptor In Keratinocytesmentioning
confidence: 99%
“…Studies by Voorhees and colleagues and Flaxman and Harper over 30 years ago demonstrated the regulation of keratinocyte proliferation by intracellular levels of cAMP, and that elevation of intracellular cAMP by catecholamine stimulation resulted in a decrease in proliferation [8,9,[63][64][65]. Work by these laboratories also suggested that a decrease in the ability of psoriatic keratinocytes to respond to beta adrenergic agonists with an increase in cAMP could be, in part, responsible for the increase in cell proliferation characteristic of the disease [66][67][68][69].…”
Section: Psoriasismentioning
confidence: 99%
“…The beta adrenergic receptor is a classic seven transmembrane G protein coupled receptor. These receptors serve as the endogenous receptor to the catecholamine hormones norepinephrine and epinephrine, and can be further subdivided into beta1, beta2, and beta3 subtypes, based on their differential pharmacological response to catecholamines and specific antagonists, as well as differences in their protein sequences [5][6][7].The first studies to suggest the presence of betaAR in the epidermis were functional ones that demonstrated an increase in levels of cAMP in keratinocytes after stimulation with non-specific betaAR agonists [8,9]. Subsequently, work using agonists and antagonists with specificity for the different adrenergic receptor subtypes demonstrated that the increase in keratinocyte…”
SynopsisBeta2 adrenergic receptors were identified in keratinocytes more than 30 years ago, but their function in the epidermis continues to be elucidated. Abnormalities in their expression, signaling pathway, or in the generation of endogenous catecholamine agonists by keratinocytes have been implicated in the pathogenesis of cutaneous diseases such as atopic dermatitis, vitiligo and psoriasis. New studies also indicate that the beta2AR also modulates keratinocyte migration, and thus can function to regulate wound re-epithelialization. This review focuses on the function of these receptors in keratinocytes and their contribution to cutaneous physiology and disease.Keywords beta-adrenergic; keratinocyte; atopic dermatitis; psoriasis; vitiligo; wound
Physiology of the beta2 adrenergic receptor in keratinocytesOf the several identified classes of adrenergic receptors (alpha and beta, and their subtypes), it is of particular interest to note that human keratinocytes, the cells the make up the majority of the epidermis, express only beta2 adrenergic receptors (beta2AR) [1][2][3][4]. The beta adrenergic receptor is a classic seven transmembrane G protein coupled receptor. These receptors serve as the endogenous receptor to the catecholamine hormones norepinephrine and epinephrine, and can be further subdivided into beta1, beta2, and beta3 subtypes, based on their differential pharmacological response to catecholamines and specific antagonists, as well as differences in their protein sequences [5][6][7].The first studies to suggest the presence of betaAR in the epidermis were functional ones that demonstrated an increase in levels of cAMP in keratinocytes after stimulation with non-specific betaAR agonists [8,9]. Subsequently, work using agonists and antagonists with specificity for the different adrenergic receptor subtypes demonstrated that the increase in keratinocyte
“…The first studies to suggest the presence of betaAR in the epidermis were functional ones that demonstrated an increase in levels of cAMP in keratinocytes after stimulation with non-specific betaAR agonists [8,9]. Subsequently, work using agonists and antagonists with specificity for the different adrenergic receptor subtypes demonstrated that the increase in keratinocyte…”
Section: Physiology Of the Beta2 Adrenergic Receptor In Keratinocytesmentioning
confidence: 99%
“…Studies by Voorhees and colleagues and Flaxman and Harper over 30 years ago demonstrated the regulation of keratinocyte proliferation by intracellular levels of cAMP, and that elevation of intracellular cAMP by catecholamine stimulation resulted in a decrease in proliferation [8,9,[63][64][65]. Work by these laboratories also suggested that a decrease in the ability of psoriatic keratinocytes to respond to beta adrenergic agonists with an increase in cAMP could be, in part, responsible for the increase in cell proliferation characteristic of the disease [66][67][68][69].…”
Section: Psoriasismentioning
confidence: 99%
“…The beta adrenergic receptor is a classic seven transmembrane G protein coupled receptor. These receptors serve as the endogenous receptor to the catecholamine hormones norepinephrine and epinephrine, and can be further subdivided into beta1, beta2, and beta3 subtypes, based on their differential pharmacological response to catecholamines and specific antagonists, as well as differences in their protein sequences [5][6][7].The first studies to suggest the presence of betaAR in the epidermis were functional ones that demonstrated an increase in levels of cAMP in keratinocytes after stimulation with non-specific betaAR agonists [8,9]. Subsequently, work using agonists and antagonists with specificity for the different adrenergic receptor subtypes demonstrated that the increase in keratinocyte…”
SynopsisBeta2 adrenergic receptors were identified in keratinocytes more than 30 years ago, but their function in the epidermis continues to be elucidated. Abnormalities in their expression, signaling pathway, or in the generation of endogenous catecholamine agonists by keratinocytes have been implicated in the pathogenesis of cutaneous diseases such as atopic dermatitis, vitiligo and psoriasis. New studies also indicate that the beta2AR also modulates keratinocyte migration, and thus can function to regulate wound re-epithelialization. This review focuses on the function of these receptors in keratinocytes and their contribution to cutaneous physiology and disease.Keywords beta-adrenergic; keratinocyte; atopic dermatitis; psoriasis; vitiligo; wound
Physiology of the beta2 adrenergic receptor in keratinocytesOf the several identified classes of adrenergic receptors (alpha and beta, and their subtypes), it is of particular interest to note that human keratinocytes, the cells the make up the majority of the epidermis, express only beta2 adrenergic receptors (beta2AR) [1][2][3][4]. The beta adrenergic receptor is a classic seven transmembrane G protein coupled receptor. These receptors serve as the endogenous receptor to the catecholamine hormones norepinephrine and epinephrine, and can be further subdivided into beta1, beta2, and beta3 subtypes, based on their differential pharmacological response to catecholamines and specific antagonists, as well as differences in their protein sequences [5][6][7].The first studies to suggest the presence of betaAR in the epidermis were functional ones that demonstrated an increase in levels of cAMP in keratinocytes after stimulation with non-specific betaAR agonists [8,9]. Subsequently, work using agonists and antagonists with specificity for the different adrenergic receptor subtypes demonstrated that the increase in keratinocyte
“…The predominant site of [3H]NA uptake is cocaine-sensitive and, since active uptake is abolished in 60HDA-treated skin, may reasonably be considered to be sympathetic nerves. This localization of uptake sites does not allow correlation of the uptake with observed oc-adrenoceptor-mediated non-vascular effects of intradermally administered NA on wool growth (Cunningham et al 1979), or with the reported epidermal p-adrenoceptor-mediated antimitotic effect of NA (Powell et al 1971).…”
Previous studies from this labOl:atory have implicated the sympathetic neurotransmitter noradrenaline (NA) in regulation of woolft'_z The current study was undertaken to investigate [3H]NA accumulation and its localization by Merino skin, and to determine the effects of gonadal and glucocorticoid steroids on such uptake.The presence of an active uptake system was demonstrated and the process was partially characterized in terms of its magnitude, time course, concentration dependence and requirement for various nutrient and ionic factors. The uptake was seen to occur predominantly into cocaine-and 6-hydroxydopamine-sensitive sites in skin from various body regions of Merino sheep. None of three steroids tested in vivo or in vitro was seen to influence the uptake process.These results do not enable us to correlate the observed [3H]NA uptake process with the previously reported effects of NA on wool growth.
“…Those in papillae include, for instance, epithelial cells and nerve fibers (e.g., Beidler, 1969;Zalewski, 1968). Adenylate cyclase is widely distributed among tissues (Sutherland et al, 1962), including mammalian skin (Brdnstad et al, 1971;Powell et al, 1971;Mier and Urselmann, 1970). The presence of activity in the control tissues without taste buds (Table I) is therefore not surprising, but may be at variance with other results of Kurihara and Koyama (1972), who found a high level of adenylate cyclase in a particulate preparation derived from a homogenate of taste papillae, but very little activity in a similar preparation from nontaste tongue epithelium.…”
Labeling of cyclic AMP of tase papillae and its responsiveness to tast stimuli has been measured using whole papillae from bovine tongue prelabeled with [ 8-(14) C] adenine. Labeling was measured in circumvallate and fungiform papillae, both of which contain taste buds, and in filiform papillae and small blocks of tongue epithelium, which are devoid of taste buds. No differences were observed in the levels of activity. The labeling of cyclic AMP of circumvallate papillae showed only small increases (12-22%) in the presence of the taste stimulus sucrose (sweet), and the stimulatory effects were not statistically significant. The increase due to sucrose was not potentiated by theophylline. No stimulation by sucrose was observed with epithelium controls. Lactose, which is a poor taste stimulus, did not stimulate labeling of cyclic AMP in taste papillae. Theophylline, caffeine, and quinine (bitter) stimulated labeling of cyclic AMP by up to 2-fold, as did L-Epinephrine. Evidence for a specific role of cyclic AMP as a second messenger in taste sensation was not obtained. It is suggested that cyclic AMP might provide a mechanistic basis for studying some of the effects of sweet and bitter compounds in mixtures.
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