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"The alpha-1 (α1) adrenergic receptor is a G protein-coupled receptor (GPCR) associated with the Gq heterotrimeric G-protein. It consists of three highly homologous subtypes, including α1A-, α1B-, and α1D-adrenergic. Catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) signal through the α1-adrenergic receptor in the central and peripheral nervous systems. There is no α1C receptor. At one time, there was a subtype known as α1C, but it was found to be identical to the previously discovered α1A receptor subtype. To avoid confusion, naming was continued with the letter D. Effects The α1-adrenergic receptor has several general functions in common with the α2-adrenergic receptor, but also has specific effects of its own. α1-receptors primarily mediate smooth muscle contraction, but have important functions elsewhere as well. The neurotransmitter norepinephrine has higher affinity for the α1 receptor than does the hormone epinephrine/adrenaline. =Smooth muscle= In smooth muscle cells of blood vessels the principal effect of activation of these receptors is vasoconstriction. Blood vessels with α1-adrenergic receptors are present in the skin, the sphincters of gastrointestinal system, kidney (renal artery) and brain.Circulation & Lung Physiology I M.A.S.T.E.R. Learning Program, UC Davis School of Medicine During the fight-or-flight response vasoconstriction results in decreased blood flow to these organs. This accounts for the pale appearance of the skin of an individual when frightened. It also induces contraction of the urinary bladder, although this effect is minor compared to the relaxing effect of β2-adrenergic receptors. In other words, the overall effect of sympathetic stimuli on the bladder is relaxation, in order to inhibit micturition upon anticipation of a stressful event. Other effects on smooth muscle are contraction in: * Ureter * Uterus (when pregnant): this is minor compared to the relaxing effects of the β2 receptor, agonists of which - notably albuterol/salbutamol - were formerly used to inhibit premature labor. * Urethral sphincter * Bronchioles (although minor to the relaxing effect of β2 receptor on bronchioles) * Iris dilator muscle Page 163 * Seminal tract, resulting in ejaculation =Neuronal= Activation of α1-adrenergic receptors produces anorexia and partially mediates the efficacy of appetite suppressants like phenylpropanolamine and amphetamine in the treatment of obesity. Norepinephrine has been shown to decrease cellular excitability in all layers of the temporal cortex, including the primary auditory cortex. In particular, norepinephrine decreases glutamatergic excitatory postsynaptic potentials by the activation of α1-adrenergic receptors. Norepinephrine also stimulates serotonin release by binding α1-adrenergic receptors located on serotonergic neurons in the raphe. Stahl, S. M. (2008). Essential Psychopharmacology Online. Retrieved October 20, 2020 from https://stahlonline-cambridge- org.offcampus.lib.washington.edu/essential_4th_chapter.jsf?page=chapter7.htm&name;=Chapter%207&title;=Antidepressant%20classes#c02598-7-76 α1-adrenergic receptor subtypes increase inhibition in the olfactory system, suggesting a synaptic mechanism for noradrenergic modulation of olfactory driven behaviors. =Other= * Both positive and negative inotropic effects on heart muscle * Secretion from salivary gland * Increase salivary potassium levels * Glycogenolysis and gluconeogenesis in liver. * Secretion from sweat glands * Contraction of the urinary bladder urothelium and lamina propria * Na+ reabsorption from kidney ** Stimulate proximal tubule NHE3 Page 787 ** Stimulate proximal tubule basolateral Na-K ATPase * Activate mitogenic responses and regulate growth and proliferation of many cells * Involved in the detection of mechanical feedback on the hypoglossal motor neurons which allow a long-term facilitation in respiration in response to repeated apneas. Signaling cascade α1-Adrenergic receptors are members of the G protein- coupled receptor superfamily. Upon activation, a heterotrimeric G protein, Gq, activates phospholipase C (PLC), which causes phosphatidylinositol to be transformed into inositol triphosphate (IP3) and diacylglycerol (DAG). While DAG stays near the membrane, IP3 diffuses into the cytosol and to find the IP3 receptor on the endoplasmic reticulum, triggering calcium release from the stores. This triggers further effects, primarily through the activation of an enzyme Protein Kinase C. This enzyme, as a kinase, functions by phosphorylation of other enzymes causing their activation, or by phosphorylation of certain channels leading to the increase or decrease of electrolyte transfer in or out of the cell. Activity during exercise During exercise, α1-adrenergic receptors in active muscles are attenuated in an exercise intensity-dependent manner, allowing the β2-adrenergic receptors which mediate vasodilation to dominate. In contrast to α2-adrenergic receptors, α1-adrenergic-receptors in the arterial vasculature of skeletal muscle are more resistant to inhibition, and attenuation of α1-adrenergic- receptor-mediated vasoconstriction only occurs during heavy exercise. Note that only active muscle α1-adrenergic receptors will be blocked. Resting muscle will not have its α1-adrenergic receptors blocked, and hence the overall effect will be α1-adrenergic-mediated vasoconstriction. Ligands ; Agonists * Cirazoline (vasoconstrictor) * Methoxamine (vasoconstrictor) * Synephrine (mild vasoconstrictor) * Etilefrine (antihypotensive) * Metaraminol (antihypotensive) * Midodrine (antihypotensive) * Naphazoline (decongestant) * Norepinephrine (vasoconstrictor) * Oxymetazoline (decongestant) * Phenylephrine (decongestant) * Pseudoephedrine (decongestant) * Tetrahydrozoline (decongestant) * Xylometazoline (decongestant) ; Antagonists * Acepromazine (antipsychotic, secondary mechanism) * Alfuzosin (used in benign prostatic hyperplasia) * Arotinolol * Carvedilol (used in congestive heart failure; it is a non-selective beta blocker) * Doxazosin (used in hypertension and benign prostatic hyperplasia) * Indoramin * Labetalol (used in hypertension; it is a mixed alpha/beta adrenergic antagonist) * Moxisylyte * Phenoxybenzamine * Phentolamine (used in hypertensive emergencies; it is a nonselective alpha-antagonist) * Prazosin (used in hypertension) * Quetiapine * Risperidone * Silodosin * Tamsulosin (used in benign prostatic hyperplasia) * Terazosin * Tiamenidine * Tolazoline * Trazodone * Trimazosin * Urapidil Various heterocyclic antidepressants and antipsychotics are α1-adrenergic receptor antagonists as well. This action is generally undesirable in such agents and mediates side effects like orthostatic hypotension, and headaches due to excessive vasodilation. See also * Adrenergic receptor References External links * Adrenergic receptors "
"Valevatn is a lake in the municipality of Sirdal in Agder county, Norway. The lake lies just north of the lake Gravatnet and a short distance west of the village of Kvæven. There are two dams on the east side of the L-shaped lake. The lake drains into the lake Gravatnet and the river Sira which runs just east of the lake. See also *List of lakes in Norway References Sirdal Lakes of Agder "
"TNT is a weekly, free magazine published in the United Kingdom, Australia and New Zealand. History The magazine was founded in September 1983, from an office on the Earls Court Road by two British Iraqi brothers, Ali and Ghadir Razuki. Their family left Iraq for the UK in 1968 when Saddam Hussein's Ba'ath Party, then led by Ahmed Hassan al-Bakr, came to power. They regularly socialised with Australians and New Zealanders, and after recognising the difficulty friends faced getting regular news and sport updates from home, the brothers, then aged 18 and 22, set about creating a weekly magazine to meet the needs of the hundreds of thousands of Aussies, Kiwis and Saffas who visit London (South Africans did not arrive in large numbers until the post- apartheid era in the early 1990s). The first edition had only 48 pages, but within several years this had increased to 350 pages, with a weekly print run of 75,000. Distribution The UK version was the first magazine to reach readers via distribution bins in key areas across London. It was also available from pubs, hostels and travel agents, then later from internet cafes. The Australian and New Zealand versions followed the same distribution methods. In the UK, it is aimed at Australians, New Zealanders and South Africans living, working and travelling in the UK (though mostly in London). In Australia, the magazine is aimed at British, Irish, European and, increasingly, North American travellers. The magazine focuses on travel, jobs, accommodation, plus news and sport from home, and offers tips on living in London (UK version) and Australasia (Australia & New Zealand versions). TNT UK also publishes a guide to the UK and Ireland for Australians, New Zealanders and South Africans planning to move to the UK or Ireland, while TNT Downunder produces a similar annual title targeting those wanting to travel (and in many cases move) to Australia, New Zealand or Fiji. Other media TNT Multimedia, which owns the UK magazine, also owns South African Times and South African Times.co.uk, and brings out quarterly teaching and finance directories, among other ad hoc supplements. TNTMagazine.com, linked to the UK magazine, was relaunched in October 2008 having previously existed under various urls. TNT Jobs - a standalone jobs board, advertises jobs in the UK, Australia and New Zealand. The magazine also runs regular travel and recruitment exhibitions for its readers, as well as an annual travel writing and photography awards competition. In 2000, TNT magazine was sold by the brothers to Trader Media Group for a sum reportedly in excess of £30 million, and in February 2008, Trader Media Group sold it on to Red Reef Media. Use of the TNT name It was originally intended to be the Independent Travel and News, however this clashed with Independent Television News, so they came up with The News and Travel – TNT. A letter was written to the Australian-founded freight company, TNT, who did not object to the new magazine’s name. However, two years later, TNT’s freight chairman, on a visit from Australia in London, snared a copy of the magazine from opposite Harrods. The magazine soon got a letter saying it could not use the TNT name. The Razuki brothers had kept TNT freight’s initial approval letter, which settled matters in their favour. In September 2013, TNT Multimedia was formally put into administration. References External links * TNTMagazine.com * SouthAfricanTimes.co.uk * Acuitycaptial.co.uk * TNTDownunder.com * TNT video on Google+ Magazine publishing companies of the United Kingdom Tourism magazines Weekly magazines published in the United Kingdom Magazines established in 1983 1983 establishments in the United Kingdom "