Recettori alfa e beta

[Vegeta]

Salve, non sapevo in che sezione del forum postare questa domanda, comunque questa mi sembra la zona adata, volevo chiedervi se per favore mi spiegate cosa sono i recettori alfa e beta e mi spiegate come funzionano, grazie in anticipo

[Antò]

Credo tu ti riferisca ai recett adrenergici (delle catecolamine).
Rendiamola semplice e molto generale: diciamo che gli alfa hanno funzione inibititrice nel rilascio di acidi grassi. Hanno funzione di "preservazione" del grasso essenziale (hanno, difatti, una maggiore espressione sull'adiposità in zone "sesso-specifiche"; basso addome e zona lombare nell'uomo. Fianchi, cosce e glutei nelle donne)
Epinefrina e norepinefrina si legano a i recettori alfa e li attivano bloccano la lipolisi (rilascio di acidi grassi) su quel determinato tessuto. Inoltre l'attivazione dei recettori alfa funge da feedback negativo nel rilascio di ACTH (ormone che strimola il rilascio da parte dei surreni dell'adrenalina).
I reccettori beta invece hanno funzione opposta, stimolano la lipolisi.
Vi è da distinguere anche fra i vari tipi di recettori alfa e beta, che vengono numerati e sono tessuto-specifici con specifiche funzioni, ma questo è noioso e nn molto importante.
Il blocco (antagonismo) dei recettori alfa porta ad un aumento del rilascio di catecolamine ed un aumento della lipolisi nei tessuti adiposi essenziali (quelli con un rapporto maggiore tra recettori alfa : beta)

[Vegeta]

E quindi se una sostanza (come l' efedrina) agisce sia sui recettori alfa che beta cosa succede????

[Anabolic]

We anto non ho capito certe cose perchè ho letto che i beta agonisti aumentano la sintesi proteica ??
poi

Originariamente inviato da Antò

diciamo che gli alfa hanno funzione inibititrice nel rilascio di acidi grassi. Hanno funzione di "preservazione" del grasso essenziale (hanno, difatti, una maggiore espressione sull'adiposità in zone "sesso-specifiche"; basso addome e zona lombare nell'uomo. Fianchi, cosce e glutei nelle donne)

Praticamente viene inibita la lipolisi nella zona basso addome e lombari nel uomo proprio dove io ho il grasso ed inoltre sta anche sui fianchi a me.

Originariamente inviato da Antò

Il blocco (antagonismo) dei recettori alfa porta ad un aumento del rilascio di catecolamine ed un aumento della lipolisi nei tessuti adiposi essenziali (quelli con un rapporto maggiore tra recettori alfa : beta)

Quali sono i tessuti adiposi essenziali?

[Bellero]

segnato...

[Guru]

Inserisco un documento riassuntivo, anche se parziale, sulla natura dei recettori.

Il tema sarà affrontato con maggiore cura nella prossima sezione sulla fisiologia.

[Vegeta]

grazie delle risposte, il mio inglese non è un gran chè ma piu o meno mi sono fatto un idea

[Anabolic]

ma io che ho il grasso nel basso adome e nei fianchi e diciamo nei fianchi verso i lombari quali sono i recettori da stimolare per la lipolisi localizzata?
Leggevo in un post di antò che lo yohimbe puo essere utilizzato anche topicamente.

[Anabolic]

oltre alla domanda sopra
Perche si dice che i B agonisti aumentano l' ipertrofia ??

[NoMoreTrouble]

Originariamente inviato da Bellero

segnato...

animale

[Bellero]

:

Originariamente inviato da NoMoreTrouble

animale

ciao ammore

[Antò]

Originariamente inviato da Anabolic

oltre alla domanda sopra
Perche si dice che i B agonisti aumentano l' ipertrofia ??

The orphan nuclear receptor, NOR-1, is a target of beta-adrenergic signaling in skeletal muscle.

Pearen MA, Ryall JG, Maxwell MA, Ohkura N, Lynch GS, Muscat GE.

Institute for Molecular Bioscience, Division of Molecular Genetics and Development, University of Queensland, St. Lucia, Queensland 4072, Australia.

beta-Adrenergic receptor (beta-AR) agonists induce Nur77 mRNA expression in the C2C12 skeletal muscle cell culture model and elicit skeletal muscle hypertrophy. We previously demonstrated that Nur77 (NR4A1) is involved in lipolysis and gene expression associated with the regulation of lipid homeostasis. Subsequently it was demonstrated by another group that beta-AR agonists and cold exposure-induced Nur77 expression in brown adipocytes and brown adipose tissue, respectively. Moreover, NOR-1 (NR4A3) was hyperinduced by cold exposure in the nur77(-/-) animal model. These studies underscored the importance of understanding the role of NOR-1 in skeletal muscle. In this context we observed 30-480 min of beta-AR agonist treatment significantly and transiently increased expression of the orphan nuclear receptor NOR-1 in both mouse skeletal muscle tissue (plantaris) and C2C12 skeletal muscle cells. Specific beta(2)- and beta(3)-AR agonists had similar effects as the pan-agonist and were blocked by the beta-AR antagonist propranolol. Moreover, in agreement with these observations, isoprenaline also significantly increased the activity of the NOR-1 promoter. Stable exogenous expression of a NOR-1 small interfering RNA (but not the negative control small interfering RNA) in skeletal muscle cells significantly repressed endogenous NOR-1 mRNA expression and led to changes in the expression of genes involved in the control of lipid use and muscle mass underscored by a dramatic increase in myostatin mRNA expression. Concordantly the myostatin promoter was repressed by NOR-1 expression. In conclusion, NOR-1 is highly responsive to beta-adrenergic signaling and regulates the expression of genes controlling fatty acid use and muscle mass.

J Biol Chem. 2005 Apr 1;280(13):12573-84.

Nur77 regulates lipolysis in skeletal muscle cells. Evidence for cross-talk between the beta-adrenergic and an orphan nuclear hormone receptor pathway.

Maxwell MA, Cleasby ME, Harding A, Stark A, Cooney GJ, Muscat GE.

Institute for Molecular Bioscience, Division of Molecular Genetics and Development, University of Queensland, St. Lucia Queensland 4072, Australia.

Skeletal muscle is a major mass peripheral tissue that accounts for approximately 40% of total body weight and 50% of energy expenditure and is a primary site of glucose disposal and fatty acid oxidation. Consequently, muscle has a significant role in insulin sensitivity, obesity, and the blood-lipid profile. Excessive caloric intake is sensed by the brain and induces beta-adrenergic receptor (beta-AR)-mediated adaptive thermogenesis. Beta-AR null mice develop severe obesity on a high fat diet. However, the target gene(s), target tissues(s), and molecular mechanism involved remain obscure. We observed that 30-60 min of beta-AR agonist (isoprenaline) treatment of C2C12 skeletal muscle cells strikingly activated (>100-fold) the expression of the mRNA encoding the nuclear hormone receptor, Nur77. In contrast, the expression of other nuclear receptors that regulate lipid and carbohydrate metabolism was not induced. Stable transfection of Nur77-specific small interfering RNAs (siNur77) into skeletal muscle cells repressed endogenous Nur77 mRNA expression. Moreover, we observed attenuation of gene and protein expression associated with the regulation of energy expenditure and lipid homeostasis, for example AMP-activated protein kinase gamma3, UCP3, CD36, adiponectin receptor 2, GLUT4, and caveolin-3. Attenuation of Nur77 expression resulted in decreased lipolysis. Finally, in concordance with the cell culture model, injection and electrotransfer of siNur77 into mouse tibialis cranialis muscle resulted in the repression of UCP3 mRNA expression. This study demonstrates regulatory cross-talk between the nuclear hormone receptor and beta-AR signaling pathways. Moreover, it suggests Nur77 modulates the expression of genes that are key regulators of skeletal muscle lipid and energy homeostasis. In conclusion, we speculate that Nur77 agonists would stimulate lipolysis and increase energy expenditure in skeletal muscle and suggest selective activators of Nur77 may have therapeutic utility in the treatment of obesity.

Beta 2-agonist fenoterol has greater effects on contractile function of rat skeletal muscles than clenbuterol.

Ryall JG, Gregorevic P, Plant DR, Sillence MN, Lynch GS.

Department of Physiology, The University of Melbourne, Melbourne, Victoria 3010, Australia.

Potential treatments for skeletal muscle wasting and weakness ideally possess both anabolic and ergogenic properties. Although the beta(2)-adrenoceptor agonist clenbuterol has well-characterized effects on skeletal muscle, less is known about the therapeutic potential of the related beta(2)-adrenoceptor agonist fenoterol. We administered an equimolar dose of either clenbuterol or fenoterol to rats for 4 wk to compare their effects on skeletal muscle and tested the hypothesis that fenoterol would produce more powerful anabolic and ergogenic effects. clenbuterol treatment increased fiber cross-sectional area (CSA) by 6% and maximal isometric force (P(o)) by 20% in extensor digitorum longus (EDL) muscles, whereas fiber CSA in soleus muscles decreased by 3% and P(o) was unchanged, compared with untreated controls. In the EDL muscles, fenoterol treatment increased fiber CSA by 20% and increased P(o) by 12% above values achieved after clenbuterol treatment. Soleus muscles of fenoterol-treated rats exhibited a 13% increase in fiber CSA and a 17% increase in P(o) above that of clenbuterol-treated rats. These data indicate that fenoterol has greater effects on the functional properties of rat skeletal muscles than clenbuterol.


Mol Reprod Dev. 2007 Oct 18

Clenbuterol increases muscle fiber size and GATA-2 protein in rat skeletal muscle in utero.

Downie D, Delday MI, Maltin CA, Sneddon AA.

Rowett Research Institute, Bucksburn, Aberdeen, Scotland, UK.

Certain beta(2)-adrenoceptor agonists, such as clenbuterol, are known to elicit a muscle-specific anabolism or hypertrophy in both normal and catabolic muscle in a wide variety of species. However, the underlying mechanism(s) of the beta(2)-agonist-induced anabolism remains unclear. This study aimed to determine the effects of clenbuterol administration in utero on skeletal muscle and to examine the underlying molecular mechanisms. Pregnant rats were fed clenbuterol (2 mg/kg diet) from Day 4 of gestation (4 dg) until weanling and fetal samples were taken from 13.5, 15.5, 17.5, and 19.5 dg and from 1d neonatal pups. Muscles were analyzed for total DNA, RNA and protein and sections examined morphologically for changes in muscle development. Western and immunohistochemical analyses were performed to identify changes in known myogenic signaling proteins. Clenbuterol increased the size of both fast and slow fibers in utero which was associated with a decreased DNArotein ratio (28%) and an increased RNANA ratio (36%). Additionally, drug treatment in utero induced a decrease in the fast:slow fiber ratio (38%). These myogenic changes were correlated with an increase in the GATA-2 hypertrophic transcription factor at both 17.5 dg (by 250%) and 19.5 dg (by 40%) in fetuses from clenbuterol treated dams. In addition, drug treatment resulted in increased membrane association of PKC-micro at 17.5 dg (325%) and increased PKC-alpha cytosolic abundance (40%) and PKC-theta membrane abundance at 19.5 dg (250%). These results are the first demonstration that beta(2)-agonists such as clenbuterol may act through upregulating the GATA-2 transcription factor and implicate certain PKC isoforms in the drug-induced regulation of skeletal muscle development.



Am J Physiol Cell Physiol. 2007 May;292(5):C1681-9.

Extracellular signal-regulated kinase pathway is differentially involved in beta-agonist-induced hypertrophy in slow and fast muscles.

Shi H, Zeng C, Ricome A, Hannon KM, Grant AL, Gerrard DE.

Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA.

The molecular mechanisms controlling beta-adrenergic receptor agonist (BA)-induced skeletal muscle hypertrophy are not well known. We presently report that BA exerts a distinct muscle- and muscle fiber type-specific hypertrophy. Moreover, we have shown that pharmacologically or genetically attenuating extracellular signal-regulated kinase (ERK) signaling in muscle fibers resulted in decreases (P < 0.05) in fast but not slow fiber type-specific reporter gene expressions in response to BA exposure in vitro and in vivo. Consistent with these data, forced expression of MAPK phosphatase 1, a nuclear protein that dephosphorylates ERK1/2, in fast-twitch skeletal muscle ablated (P < 0.05) the hypertrophic effects of BA feeding (clenbuterol, 20 parts per million in water) in vivo. Further analysis has shown that BA-induced phosphorylation and activation of ERK occurred to a greater (P < 0.05) extent in fast myofibers than in slow myofibers. Analysis of the basal level of ERK activity in slow and fast muscles revealed that ERK1/2 is activated to a greater extent in fast- than in slow-twitch muscles. These data indicate that ERK signaling is differentially involved in BA-induced hypertrophy in slow and fast skeletal muscles, suggesting that the increased abundance of phospho-ERK1/2 and ERK activity found in fast-twitch myofibers, compared with their slow-twitch counterparts, may account, at least in part, for the fiber type-specific hypertrophy induced by BA stimulation. These data suggest that fast myofibers are pivotal in the adaptation of muscle to environmental cues and that the mechanism underlying this change is partially mediated by the MAPK signaling cascade.





Am J Physiol Cell Physiol. 2000 Nov;279(5):C1558-63.

Effects of unweighting and clenbuterol on myosin light and heavy chains in fast and slow muscles of rat.

Stevens L, Firinga C, Gohlsch B, Bastide B, Mounier Y, Pette D.

Laboratoire de Plasticité Neuromusculaire, Université des Sciences et Technologies de Lille, F-59655 Villeneuve d'Ascq, France.

To investigate the plasticity of slow and fast muscles undergoing slow-to-fast transition, rat soleus (SOL), gastrocnemius (GAS), and extensor digitorum longus (EDL) muscles were exposed for 14 days to 1) unweighting by hindlimb suspension (HU), or 2) treatment with the beta(2)-adrenergic agonist clenbuterol (CB), or 3) a combination of both (HU-CB). In general, HU elicited atrophy, CB induced hypertrophy, and HU-CB partially counteracted the HU-induced atrophy. Analyses of myosin heavy (MHC) and light chain (MLC) isoforms revealed HU- and CB-induced slow-to-fast transitions in SOL (increases of MHCIIa with small amounts of MHCIId and MHCIIb) and the upregulation of the slow MHCIa isoform. The HU- and CB-induced changes in GAS consisted of increases in MHCIId and MHCIIb ("fast-to-faster transitions"). Changes in the MLC composition of SOL and GAS consisted of slow-to-fast transitions and mainly encompassed an exchange of MLC1s with MLC1f. In addition, MLC3f was elevated whenever MHCIId and MHCIIb isoforms were increased. Because the EDL is predominantly composed of type IID and IIB fibers, HU, CB, and HU-CB had no significant effect on the MHC and MLC patterns.

[Anabolic]

Anto ma questi B agonsti come il clen, efe da quello che leggo stimolano il rilascio NA, ma e l' Efe e ilClen che si legano ai recettori adrenergici o il NA che stimolano sono un po confuso.
O forse fanno tutte e due le cose

[Guru]

Esatto, che io sappia avvengono entrambe le cose, stimolazione del rilascio di NA ed azione diretta.
Antonio sarà sicuramente più preciso

[Antò]

L'efedrina ha azione agonista sui recettori anche se lieve, la sua "forza" la esplica aumentando il "fire rate" delle sinapsi nervose, potenzia l'effetto dell'adrenalina e della noradrenalina. A livello encefalico agisce da agonista sui recettori della noradrenalina e d aumenta il rilascio di dopamina.
Il clen è un diretto e specifico agonista dei recettori beta2adrenergici, difatti diminuisce o meglio inibisce il rilascio delle catecolamine e tende a desensibillare i recettori, cosa che nn fa, in parte, l'efedrina o cmq a questa serve + tempo per inibire del tutto il rilascio di ACTH e desensibilizzare i recettori poichè nn è un forte legante.