Characterization of alpha-2-adrenoceptor subtypes involved in catecholamine release from the adrenal medulla of mice

• Type: Other Publications
• Date: 2006

Authors

moura, e (Author) Other; afonso, j (Author) Other; hein, l (Author) Other; vieira-coelho, ma (Author) FMUP

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-004-FKH

DOI: 10.1038/sj.bjp.0706950

Abstract (EN): Background and purpose: This study was carried out to elucidate which ¿ 2-adrenoceptor subtypes mediated the inhibition of noradrenaline and adrenaline release from the adrenal medulla of mice. Experimental approach: Isolated adrenal medullae from wild-type and ¿ 2A, ¿ 2B and ¿ 2C-adrenoceptor knockout (KO) mice were placed in superfusion chambers. Catecholamine overflow was evoked by 1,1-dimethyl-4-phenylpiperazinium (500 ¿M) in absence or in presence of the ¿ 2-adrenoceptor agonist medetomidine. The effect of medetomidine was tested in presence of the ¿-adrenoceptor antagonists rauwolscine, WB 4101, spiroxatrine, phentolamine and prazosin. Key results: In wild-type mice, medetomidine reduced noradrenaline and adrenaline overflow in a concentration-dependent manner (EC 50 in nM: 1.54 and 1.92; E max in % of inhibition: 91 and 94, for noradrenaline and adrenaline, respectively). The pK D values of the antagonists for noradrenaline overflow did not correlate with pK D values at ¿ 2A, ¿ 2B, or ¿ 2C binding sites. The pK D values of the antagonists for adrenaline overflow correlated positively with pK D values at ¿ 2C binding sites (opossum kidney cells). The effect of medetomidine (100 nM) on noradrenaline overflow was significantly reduced in all three ¿ 2KO mice (57, 54, 44 % inhibition, for ¿ 2A, ¿ 2B, and ¿ 2C, respectively), whereas the effect of medetomidine on adrenaline overflow was greatly reduced in ¿ 2CKO mice (14 % inhibition). Conclusions and implications: In the adrenal medulla of mice, all three ¿ 2-adrenoceptor subtypes (¿ 2A, ¿ 2B, and ¿ 2C) play an equal role in the inhibition of noradrenaline overflow, whereas the ¿ 2C-adrenoceptor is the predominant ¿ 2- adrenoceptor subtype involved in the inhibitory mechanism controlling adrenaline overflow.

Language: English

Type (Professor's evaluation): Scientific