Pi-adrenergic receptors

Relatively selective stimulation of Pi-adrenergic receptors can be achieved with dobutamine. This is a racemic drug of which both isomers activate the Pi-receptor, and in addition the (-) isomer activates ( -receptors whereas the (+) isomer activates p2-receptors the simultaneous activation of ai- and p2-receptors results in no major net effect on peripheral resistance, and thus the overall cardiovascular effects are mediated by Pi-stimulation leading to increases in cardiac contractility and output. Dobutamine is used for the short-term treatment of acute cardiac failure and for diagnostic purposes in stress echocardiography. 

Rochais F, Vilardaga JP, Nikolaev VO et al (2007) Realtime optical recording of Pi-adrenergic receptor activation reveals supersensitivity of the Arg389 variant to carvedi-lol. J Clin Invest 117229-235... 

Sympathetic nerve activity causes an increase in blood pressure through many mechanisms, including an increase in cardiac activity and vasoconstriction. Activation of the sympathetic system also causes the stimulation of Pi-adrenergic receptors on the renin-producing cells, which promotes renin release. 

Green S, Turki J, Innis M, Liggett S. Amino-terminal polymorphisms of the human pi-adrenergic receptor impart distinct agonist-promoted regulatory properties. Biochemistry 1994 33 9414— 9419. 

The answer is b. (Katzung, p 166.) Propranol nonspecifically blocks Pi-adrenergic receptors. It lowers blood pressure primarily by decreasing cardiac output. 

There is also evidence of autonomic involvement in VKC. Muscarinic and Pi-adrenergic receptors are altered in the inflamed conjimctiva. Also, muscarinic receptor stimulation activates the goblet cells to produce mucus. 

Pi-Adrenergic receptor (ADRB1) 10q24-q26 G389R (C-terminus) t Basal and agonist-dependent G coupling—gain of function... 

Nebivolol is a selective pi adrenergic receptor antagonist with nitric oxide-mediated vasodilatory properties. Nebivolol modulates amyloid-p protein precursor processing in vitro and in vivo. Nebivolol is brain bioavailable and can be readily detected in the brain following 3 weeks of treatment at a dose of 1 mg/kg/day. Chronic nebivolol treatment of Tg2576 mice with amyloid neuropathology reduced brain amyloid content but failed to improve cognitive function [528],... 

Drugs such as metoprolol that target the pi-adrenergic receptor arc popular treatments for hypertension. 

Israel E, Drazen JM, Liggett SB, et al The effect of polymorphisms of the pi-adrenergic receptor on the response to regular use of albuterol in asthma. Am J Respir Crit Care Med 2000 162 75-80. (Ila)... 

Ritodrine has an effect on beta (p)2-adrenergic receptors, principal diose diat innervate die utenis. Stimulation of diese P2-adrenergic receptors inlnbits uterine smoodi muscle contractions. The Pi-adrenergic receptors are located in die heart and are not stimulated by ritodrine when administered as prescribed. Ritodrine is used to... 

Dobutamine increases cAMP production by binding to Pi adrenergic receptors. 

Atenolol (Tenormin) Preferentially blocks pi adrenergic receptors. Decreases heart rate and output and i renin release. Less bronchoconstriction than agents which bind to P2 receptors Good starting therapy for mild to moderate hypertension Further suppresses tailing heart. CNS sedation and depression. 

Mason, D.A., et al. A gain-of-function polymorphism in a G-protein coupling domain of the human Pi-adrenergic receptor. J. Biol. Chem. 1999, 274, 12670-12674. 

Liggett, S.B., et al. A polymorphism within a conserved Pi-adrenergic receptor motif alters cardiac function and P-blocker response in human heart failure. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 11288-11293. 

Wame T, Moukhametzianov R, Baker JG et al (2011) The stmctural basis for agonist and partial agonist action on a pi-adrenergic receptor. Nature 469 241-244... 

Figure 2.1 Crystal structure of (a) bovine (PDB accession number ICZM) [12] and (b) squid I Z73) [13] rhodopsin bound to the full inverse agonist c/s-retinal (in spheres), and (c) the pi-adrenergic receptor bound to the partial inverse agonist carazolol (in spheres) (2RH1) [17, 19].

Antagonists yohimbine > phentolamine > prazosin Pi-adrenergic receptors... 

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