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Measurement of 3‐methoxy‐4‐hydroxyphenylglycol (MHPG) in mouse brain by h.p.l.c. with electrochemical detection, as an index of noradrenaline utilisation and presynaptic α 2 ‐adrenoceptor function
Author(s) -
Heal D.J.,
Prow M.R.,
Buckett W.R.
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb11852.x
Subject(s) - idazoxan , endocrinology , prazosin , chemistry , pargyline , medicine , yohimbine , agonist , phenylephrine , alpha (finance) , antagonist , receptor , serotonin , blood pressure , construct validity , nursing , patient satisfaction
1 A novel method for measurement of 3‐methoxy‐4‐hydroxyphenylglycol (MHPG) in mouse brain by use of high performance liquid chromatography (h.p.l.c.) with electrochemical detection is described. This technique incorporates an ethyl acetate purification procedure and uses 3‐hydroxy‐4‐methoxyphenylglycol (iso‐MHPG) as the internal standard. 2 Inhibition of monoamine oxidase by injection of tranylcypromine (5 and 10 mg kg −1 ) or pargyline (50 and 100 mg kg −1 ) markedly decreased brain MHPG concentrations. After injection of the tyrosine hydroxylase inhibitor, α‐methyl‐ p ‐tyrosine (200 mg kg −1 ), there were time‐dependent linear decreases in the concentrations of noradrenaline and MHPG in mouse brain. In addition, a very good correlation ( r = 0.95, n = 30; P < 0.001) was found between the concentrations of noradrenaline and MHPG present in the brains of the same mice after α‐methyl‐ p ‐tyrosine treatment. 3 Mouse brain MHPG concentrations were dose‐dependently reduced after administration of the α 2 ‐adrenoceptor agonist, clonidine (1–3000 μg kg −1 ), and elevated by the antagonists, idazoxan (1 and 5 mg kg −1 ), and yohimbine (1 and 5 mg kg −1 ). Intracerebroventricular injection of the α 1 ‐adrenoceptor agonist, phenylephrine (5–50 μg) dose‐dependently increased MHPG levels. The α 1 ‐adrenoceptor antagonist, prazosin, had no effect at the moderate dose of 1 mg kg −1 , but increased MHPG concentrations at 5 mg kg −1 . The β‐adrenoceptor agonist, clenbuterol (10–1000 μg kg −1 ) and the antagonist, pindolol (1 and 5 mg kg −1 ), were both without effect. 4 The decrease in brain MHPG concentrations induced by clonidine (100 μg kg −1 ) was prevented by prior injection of 1 mg kg −1 of idazoxan or yohimbine, but not by prazosin or pindolol. 5 MHPG levels were decreased after administration of the noradrenaline reuptake inhibitor desipramine (5 and 10 mg kg −1 ) and the non‐selective monoamine reuptake inhibitors, sibutramine HCl (BTS 54 524; 1 and 3 mg kg −1 ) and amitryptyline (5 mg kg −1 ). However, the selective 5‐hydroxytryptamine reuptake inhibitor, zimeldine (5 and 10 mg kg −1 ), was without effect. Dexamphetamine (1 and 5 mg kg −1 ) and methamphetamine (1 and 5 mg kg −1 ) both decreased brain MHPG concentrations in a dose‐related fashion. 6 Overall the data show that MHPG can be used as a functional index of both presynaptic α 2 ‐adrenoceptor activity and noradrenaline turnover and utilisation.