A2-autoreceptors

Trendelenburg AU, Hein L, Gaiser EG, Starke K (1999) Occurrence, pharmacology and function of presynaptic a2-autoreceptors in a2An) a< cnoceptor-deficient mice. Naunyn-Schmiedeberg s Arch Pharmacol 360 540-551... 

Trendelenburg AU, Limberger N, Starke K (1993) Presynaptic a2-autoreceptors in brain cortex a2D in the rat and U2a in the rabbit. Naunyn-Schmiedeberg s Arch Pharmacol 348 35-45... 

EP3 receptor is activated first and the H3 receptor is activated subsequently, the effect mediated via the H3 receptor is attenuated. The interactions between the three receptors have been shown in the following studies H3 and a2, ref. 35 H3 and EP3, ref. 30 a2 and EP3, ref. 46. It is so far not known whether activation of the EP3 receptor also affects the effect mediated via the a2-autoreceptor activated subsequently. Abbreviations AP, action potential Hist, histamine NA, noradrenaline PG Ej, E2, prostaglandins Ej and E2. 

In addition to the presynaptic a2 autoreceptor subtypes which were identified in CNS and sympathetic nerves, studies in gene-targeted mice uncovered a2cAR as autoreceptors controlling catecholamine release from chromaffin cells (Brede... 

Trendelenburg AU, Meyer A, Klebroff W, Guimaraes S, Starke K (2003) Crosstalk between presynaptic angiotensin receptors, bradykinin receptors and a2-autoreceptors in sympathetic neurons a study in a2-adrenoceptor-deficient mice. Br J Pharmacol 138 1389-1402 Uchida H, Takeuchi H, Suzuki T, Nomura K, Watanabe K, Kashima H (2005) Combined treatment with sulpiride and paroxetine for accelerated response in patients with major depressive disorder. J Clin Psychopharmacol 25 545-51... 

Allgaier C, Hertting G, Ktigelgen OV (1987) The adenosine receptor-mediated inhibition of noradrenaline release possibly involves an N-protein and is increased by a2-autoreceptor blockade. Br J Pharmacol 90 403-12... 

Mota A, Guimaraes S (2003) Influence of a2-autoreceptor-stimulation on the facilitation by angiotensin II and bradykinin of noradrenaline release. Naunyn-Schmiedberg s Arch Pharmacol 368 443-7... 

LimbergerN, Trendelenburg AU, Starke K. Pharmacological characterization of presynaptic a2-autoreceptors in rat submax illary gland and heart atrium. BrJ Pharmacol 1992 107 246-255. 

Trendelenburg AU, Sutej I, Wahl CA, Molderings GJ, Rump LC, Starke K. A reinvestigation of questionable subclassifications of presynaptic a2-autoreceptors rat vena cava, rat atria, human kidney and guinea-pig urethra. Naunyn Schmiede-bergs Arch Pharmacol 1997 356 721-737. 

Feuerstein TJ, Huber B, Vetter J, Aranda H, Van V, LimbergerN. Characterization of the a2-adrenoceptor subtype, which functions as a2-autoreceptor in human neocortex. J Pharmacol Exp Ther 2000 294 356-362. 

Trendelenburg AU, Klebroff W, Hein L, Starke K. A study of presynaptic a2-autoreceptors in (Xja/d-, oc2B- and a2C-adrenoceptor-deficient mice. Naunyn Schmie-debergs Arch Pharmacol 2001 364 117-130. 

CNS Autoreceotors for Norepinephrine (NE) - Though the concept of autoinhibition of NE release is not universally accepted,the consensus is that release of NE from sympathetic nerves is modulated through inhibitory a2 autoreceptors. By contrast, somadendritic a2-adreno-ceptors of central noradrenergic neurons inhibit firing.Release of H-amezinium from rat cortical noradrenergic axons has been advanced as a model for the study of the a2-autoreceptor hypothesis. There are a number of mechanisms possible for the link between presynaptic a2 adrenoceptor activation and transmitter release, in which a pivotal role for Ca2+ has been established.3.8 (tore recent data implicates inhibition of adenylate cyclase with receptor activation and subsequent attenuation of transmitter release. 

Irrespective of the mechanism of action of tricyclic antidepressants, antagonists of a2 autoreceptors per se might have a beneficial effect in depressive illness, since they facilitate noradrenergic neurotransmission. Phenoxybenzamine, dihydroergotamine and yohimbine, but not the selective ai adrenoceptor antagonist prazosin, have been shown to be synergistic with several antidepressants in decreasing B-adrenoceptor density in rat cerebral cortex.Thus combined administration of an a2 adrenoceptor blocker with other antidepressants may provide a rapid onset therapy.RS 21361 produces a more rapid onset of B-adrenoceptor desensitization by itself than desipramine. 

Elevated central NE activity (e.g. in the locus ceruleus) is an important correlate of human anxiety, though not the sole one. The beneficial effects of clonidine as an antianxiety agent in humans could result from its inhibitory action on NE activity by stimulation of a2-autoreceptors.The observation that yohimbine is anxio-genic in humans is in accord with this hypothesis. ... 

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