Posted by zeugma on February 20, 2006, at 15:31:34
In reply to Re: NRIs are infact dopamine uptakin inhibitors ? » SLS, posted by zeugma on February 20, 2006, at 14:48:06
given that we have been discussing the promiscuity of transporters for substrates: the D4 receptor is quite promiscuous as well:
1: Eur J Pharmacol. 2006 Feb 15;531(1-3):20-4. Epub 2006 Jan 19.
[(35)S]GTPgammaS binding at the human dopamine D4 receptor variants hD4.2, hD4.4 and hD4.7 following stimulation by dopamine, epinephrine and norepinephrine.Czermak C, Lehofer M, Liebmann PM, Traynor J.
Department of General Psychiatry I, Sigmund Freud Clinics Graz, Wagner Jauregg Platz 1, 8053 Graz, Austria; Institute of Pathophysiology, Medical University of Graz, Heinrichstr. 31a, 8010 Graz, Austria.
Aim of the present study was to investigate possible differences between the human dopamine D4 receptor 48 bp polymorphism variants hD4.2, hD.4. and hD4.7 in agonist stimulated [(35)S]GTPgammaS binding, to investigate dopamine D4 receptor sodium sensitivity and to further characterize norepinephrine and epinephrine agonism at this receptor. G-protein activation at the receptor variants hD4.2, hD4.4 and hD4.7 expressed in CHO-K1 cells, following stimulation by dopamine, norepinephrine and epinephrine, was investigated using the [(35)S]GTPgammaS assay at experimental conditions of 10 and 100 mM sodium, respectively. Dopamine displayed a 2 fold higher potency of stimulating [(35)S]GTPgammaS binding at the hD4.2, compared to the hD4.4 and hD4.7 at 10 mM sodium. A significant difference in sodium sensitivity of basal [(35)S]GTPgammaS binding was found, with the hD4.7 being 1.7 fold more sensitive than the hD4.4 and 2.5 fold more sensitive than the hD4.2. Norepinephrine and epinephrine both produced concentration-dependent increases in [(35)S]GTPgammaS binding at all three receptor variants, and epinephrine showed only 2 fold less potency than dopamine. The present results are in certain line with previous reports of functional 2-3 fold differences between the dopamine D4 receptor variants. Agonism of norepinephrine and epinephrine at the dopamine D4 receptor may indicate an important way of cross-reactivity among the different monoamine neurotransmitter systems.
It's interesting that the 7-repeat polymorphism of the D4 receptor is the one most associated with ADHD symptomology, and also with methylphenidate resistance (1.7 mg/kg is required to bring about satisfactory improvement in symptoms with this polymorphism), consonant with my experience, in which over 1 mg/kg destroyed my appetite and made me severely anxious, but did not produce the improvement that a standard dose of atomoxetine did.
I've felt for a long time that I am more responsive to adrenergic than dopaminergic meds.
-z
poster:zeugma
thread:611154
URL: http://www.dr-bob.org/babble/20060219/msgs/611485.html