PMID- 6138110
OWN - NLM
STAT- MEDLINE
DCOM- 19831220
LR  - 20190511
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 75
IP  - 2
DP  - 1982 Feb
TI  - [3H]-guanfacine: a radioligand that selectively labels high affinity 
      alpha2-adrenoceptor sites in homogenates of rat brain.
PG  - 401-8
AB  - [3H]-guanfacine (N-amidino-2-(2,6-dichloro 3[3H] phenyl) acetamide hydrochloride; 
      24.2 Ci/mmol) has been used as a radioligand in homogenates of rat cerebral 
      cortex. Specific binding of [3H]-guanfacine was linear with respect to tissue 
      concentration (2.5-15 mg/ml), saturable and not markedly affected in the pH range 
      6.5-8.0. Analysis of the saturation of [3H]-guanfacine binding using an iterative 
      least squares fitting procedure gave best fits to a single site model. 
      [3H]-guanfacine binding was of high affinity (Kd 1.77 +/- 0.24 nM; n = 8) to a 
      population of non interacting sites (nH 0.99 +/- 0.02; n = 8) with a density of 
      118.2 +/- 8.4 fmol/mg protein (n = 8). Highest levels of binding were achieved in 
      cerebral cortex followed by thalamus greater than hypothalamus greater than 
      medulla/pons greater than spinal cord greater than striatum greater than 
      cerebellum. Binding was stereoselective with regard to the (-)-isomer of 
      noradrenaline and the order of potency for displacement of [3H]-guanfacine by 
      agonists was naphazoline greater than clonidine greater than (-)-adrenaline 
      greater than (-)-alpha methylnoradrenaline greater than (-)-noradrenaline greater 
      than (+/-)-alpha-methylnoradrenaline greater than (+)-noradrenaline greater than 
      methoxamine greater than (+)-adrenaline greater than phenylephrine and by 
      antagonists was phentolamine greater than dihydroergocryptine greater than 
      piperoxane greater than yohimbine greater than prazosin greater than labetalol 
      greater than indoramin suggested binding to alpha 2-adrenoceptors. The monovalent 
      cations Na+ and K+ and also guanosine 5'-triphosphate (GTP) produced 
      concentration-dependent inhibition whereas the divalent cations Ca2+, Mg2+, and 
      Mn2+ first enhanced, then inhibited [3H]-guanfacine binding. Na+ (150 mM) or GTP 
      (100 microM) produced marked reductions and Mn2+ (5 mM) marked increases in the 
      number of receptor sites labelled by [3H]-guanfacine. 9 It is concluded that 
      [3H]-guanfacine preferentially labels a high affinity state of the alpha 2- 
      adrenoceptor in homogenates of rat cerebral cortex.
FAU - Jarrott, B
AU  - Jarrott B
FAU - Louis, W J
AU  - Louis WJ
FAU - Summers, R J
AU  - Summers RJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Adrenergic alpha-Agonists)
RN  - 0 (Guanidines)
RN  - 0 (Phenylacetates)
RN  - 0 (Receptors, Adrenergic, alpha)
RN  - 10028-17-8 (Tritium)
RN  - 30OMY4G3MK (Guanfacine)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - 9NEZ333N27 (Sodium)
RN  - MN3L5RMN02 (Clonidine)
SB  - IM
MH  - Adrenergic alpha-Agonists/*metabolism
MH  - Animals
MH  - Brain/*metabolism
MH  - Clonidine/metabolism
MH  - Female
MH  - Guanfacine
MH  - Guanidines/*metabolism
MH  - Guanosine Triphosphate/pharmacology
MH  - In Vitro Techniques
MH  - Male
MH  - Phenylacetates/*metabolism
MH  - Radioligand Assay
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Receptors, Adrenergic, alpha/*metabolism
MH  - Sodium/pharmacology
MH  - Tritium
PMC - PMC2071608
EDAT- 1982/02/01 00:00
MHDA- 1982/02/01 00:01
PMCR- 1983/02/01
CRDT- 1982/02/01 00:00
PHST- 1982/02/01 00:00 [pubmed]
PHST- 1982/02/01 00:01 [medline]
PHST- 1982/02/01 00:00 [entrez]
PHST- 1983/02/01 00:00 [pmc-release]
AID - 10.1111/j.1476-5381.1982.tb08801.x [doi]
PST - ppublish
SO  - Br J Pharmacol. 1982 Feb;75(2):401-8. doi: 10.1111/j.1476-5381.1982.tb08801.x.