Alpha! receptors

Tachykinin NK2 receptor TK NK2r Neurokinin-2 receptor, neurokinin A receptor, substance K receptor, neurokinin-alpha receptor, Neuromedin L receptor... 

Alpha receptors are the most abundant of the adrenergic receptors. Of the two subtypes, a,-receptors are more widely distributed on the effector tissues these receptors tend to be excitatory. For example, stimulation of aj-receptors causes contraction of vascular smooth muscle, resulting in vasoconstriction. 

O Brien, D.P. et al., Tumor necrosis factor alpha receptor is important for survival from Streptococcus pneumoniae infections, Infect. Immun., 67, 595, 1999. 

Peroutka, S.J., U Prichard, D.C., Greenberg, D.A. and Snyder, S.H. (1977) Neuroleptic drug interactions with norepinephrine alpha receptor binding sites in rat brain. Neuropharmacology, 16, 549-556. 

This means that even substances administered to the periphery of the body display an effect on the CNS which can no longer be observed later on. Clonidine induces sleep in these animals, as described by ZAIMIS (49), FUGNER and HOEFKE (50) and by DELBARRE and SCHMITT (51). Noradrenaline, as well as a-methylnoradrenaline, which cannot permeate the blood-brain barrier in older animals, cause sleep. This effect could be inhibited with phentolamine in the case of noradrenaline and also in the case of clonidine (FUGNER (52)). Therefore it may be assumed, that here again central adrenergic alpha-receptors are involved. 

Chatterjee, M. and Wu, S., 2001, Involvement of Fas receptor and not tumor necrosis factor-alpha receptor in ultraviolet-induced activation of acid sphingomyelinase. Mol. Carcinog. 30 47-55. 

Fabris, M., Tolusso, B., Di Poi, E., Assaloni, R., Sinigaglia, L., and Ferraccioli, G. (2002) Tumor necrosis factor-alpha receptor II polymorphism in patients from southern Europe with mild-moderate and severe rheumatoid arthritis. Journal of Rheumatology. 29, 1847-1850. 

Buescher, E. S., and Williams-Koeppen, P. (1998). Soluble tumor necrosis factor-alpha (TNF-alpha) receptors in human colostrum and milk bind to TNF-alpha and neutralize TNF-alpha bioactivity. Pediatr. Res. 44, 37—42. 

Geriatric Considerations - Summary Discontinuation of clonidine is likely to require a slow taper. If the patient is receiving a concomitant beta-blocker, the beta-blocker must be tapered and discontinued before discontinuing clonidine. Clonidine discontinuation in the presence of a beta-blocker can lead to severe hypertension and cardiovascular events due to unopposed alpha-receptor stimulation. CNS effects often preclude its use in older adults. A higher clonidine dose (0.4 mg/day) is generally needed to control peri- or postmenopausal vasomotor symptoms however, adverse effects often make it difficult to achieve effective doses. 

Mechanism of Action A vasopressor that forms the active metabolite desglymido-drine, an alphaj-agonist, activating alpha receptors of the arteriolar and venous vasculature. Therapeutic Effect Increases vascular tone and BP. 

Mechanism of Action Phenylephrine is a powerful postsynaptic alpha-receptor stimulant with little effect on the beta receptors of the heart, lacking chronotropic and... 

Mecfianism of Action Phenylephrine HCl is an alpha-receptor sympathetic agonist used in local ocular disorders because of its vasoconstrictor and mydriatic action. It exhibits rapid and moderately prolonged action, and it produces little rebound vasodilatation. Systemic side effects are uncommon. Therapeutic Effect Vasoconstriction and pupil dilation. 

The mechanisms by which 2-PAM exerts its cardiac effects have been studied in experimental animals. At least three classes of action have been attributed to the effects of altered calcium metabolism on autonomic ganglia. A sympathomimetic action of 2-PAM was postulated to explain the increase in blood pressure and the augmented myocardial contractility by one or more of the following mechanisms 2-PAM may not block the release of the endogenous compounds, but may prevent the uptake of catecholamine 1 it may stimulate the release of norepinephrine it Increases myocardial contractility by directly stimulating beta receptors and it increases blood pressure by directly stimulating alpha receptors. 5... 

The catecholamines produce their action by direct combination with receptors located on the cell membrane. In 1948, Ahlquist divided the adrenergic receptors into two main groups - alpha and beta. The alpha receptor stimulation produces excitatory effect and beta receptor stimulation usually produces inhibitory effect. 

Alpha receptors There are two major groups of alpha receptors, and a. Activation of postsynaptic receptors increases the intracellular concentration of calcium by activation of a phospholipase G in the cell membrane via G protein, receptor is responsible for inhibition of renin release from the kidney and for central a-adrenergically mediated blood pressure depression. 

Eye The radial pupillary dilator muscle of the iris contains alpha-receptors activation by drugs causes mydriasis. 

It is a vasopressor agent with some structural similarity to adrenaline and has a powerful alpha receptor stimulant action. The pressor response is accompanied by reflex bradycardia. It is used as a nasal decongestant and mydriatic agent and also in the treatment of paroxysmal supraventricular tachycardia. 

It is a potent alpha-adrenergic blocking agent and only haloalkylamine used clinically. It effectively prevents the responses mediated by alpha receptors and diastolic blood pressure tends to decrease. It interferes with the reflex adjustment of blood pressure and produces postural hypotension. It increases the cardiac output and decreases the total peripheral resistance. It also antagonizes cardiac arrhythmias provoked by catecholamines. Apart from these effects, phenoxybenzamine has other actions also e.g. antagonism of acetylcholine, histamine, 5-hydroxytryptamine (serotonin). However, the vasodilatation produced by phenoxybenzamine is because of alpha blockage. Adverse reactions are miosis, dryness of mouth, inhibition of ejaculation, palpitation, nasal stuffiness and in higher doses, postural hypotension and reflex bradycardia. 

Benign prostate hypertrophy Alpha receptor blockers increase urinary flow rate and causing more complete emptying of urinary bladder in benign prostate hypertrophy patients. 

Adrenergic blocking effect antagonists, specially of phenothiazine subgroups have weak alpha-receptor blocking effect. 

TNF-alpha receptor-immune globlulin G1 Fc fusion protein,... 

Crews FJ, Smith CB. Presynaptic alpha receptor subsensitivity after long-term antidepressant treatment. Science 1978 202 322-324. 

Alpha receptors are widely expressed in vascular beds, and their activation leads to arterial and venoconstriction. Their direct effect on cardiac function is of relatively less importance. A relatively pure agonist such as phenylephrine increases peripheral arterial resistance and decreases venous capacitance. The enhanced arterial resistance usually leads to a dose-dependent rise in blood pressure (Figure 9-... 

Alpha-receptor activation in the ductus deferens, seminal vesicles, and prostate plays a role in normal ejaculation. The detumescence of erectile tissue that normally follows ejaculation is also brought about by norepinephrine (and possibly neuropeptide Y) released from sympathetic nerves. Alpha activation appears to have a similar detumescent effect on erectile tissue in female animals. 

BASIC PHARMACOLOGY OF THE ALPHA-RECEPTOR ANTAGONIST DRUGS... 

Blockade of receptors in other tissues elicits miosis (small pupils) and nasal stuffiness. Alpha receptors are expressed in the base of the bladder and the prostate, and their blockade decreases resistance to the flow of urine. Alpha blockers, therefore, are used therapeutically for the treatment of urinary retention due to prostatic hyperplasia (see below). Individual agents may have other important effects in addition to -receptor antagonism (see below). 

Alpha-receptor antagonists are most useful in the preoperative management of patients with pheochromocytoma (Figure 10-... 

Alpha-receptor-blocking drugs do not seem to be effective in the treatment of peripheral vascular occlusive disease characterized by morphologic changes that limit flow in the vessels. Occasionally, individuals with Raynaud s phenomenon and other conditions involving excessive reversible vasospasm in the peripheral circulation do benefit from prazosin or phenoxybenzamine, although calcium channel blockers may be preferable for most patients. 

Alpha-receptor blocking effects can be demonstrated for many Hi antagonists, especially those in the phenothiazine subgroup, eg, promethazine. This action may cause orthostatic hypotension in susceptible individuals. Beta-receptor blockade is not observed. Serotonin-Blocking Action... 

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