TY - JOUR
T1 - Striatal muscarinic receptors
T2 - Regulation by dopaminergic agonists
AU - Ehlert, Frederick J.
AU - Roeske, William R.
AU - Yamamura, Henry I.
N1 - Funding Information:
Portions of this work were supported by United States Public Health Service grants MH-27257, MH-30626, and Program Project Grant HL-20984. H.I.Y. is a recipient of a USPHS RSDA, Type II (MH-O0095), from the National Institute of Mental Health. W.R.R. is a recipient of a USPHS RSDA (HL-00776) from the National Heart Lung and Blood Institute.
PY - 1981/5/21
Y1 - 1981/5/21
N2 - The effects of apomorphine on the binding properties of striatal muscarinic receptors were investigated using the specific muscarinic antagonist, [3H](-)3-quinuclidinyl benzilate ([3H](-)QNB). When binding measurements were made in 50 mM sodium/HEPES buffer, pH 7.4, containing Mg+2, the binding of [3H](-)QNB was consistent with the presence of two binding sites; 57% of the sites had a high affinity dissociation constant of 0.030 nM whereas the remaining sites had a low affinity dissociation constant of 0.64 nM. Apomorphine (1.0 μM) enhanced the binding of [3H](-)QNB by an apparent conversion of low to high affinity sites. A variety of other agents were screened for their ability to enhance [3H](-)QNB binding, and a pattern generally consistent with a dopaminergic effect was observed although some evidence for a β-adrenergic effect was demonstrable. The potent neuroleptics haloperidol, spiperone and sulpiride failed to antagonize the apomorphine enhancement of [3H](-)QNB binding as well as some adrenergic antagonists. However, the potent inhibitors of the dopamine-sensitive adenylate cyclase, α-flupenthixol and fluphenazine, specifically blocked the apomorphine enhancement of [3H](-)QNB binding with Ki values of approximately 0.1 μM.
AB - The effects of apomorphine on the binding properties of striatal muscarinic receptors were investigated using the specific muscarinic antagonist, [3H](-)3-quinuclidinyl benzilate ([3H](-)QNB). When binding measurements were made in 50 mM sodium/HEPES buffer, pH 7.4, containing Mg+2, the binding of [3H](-)QNB was consistent with the presence of two binding sites; 57% of the sites had a high affinity dissociation constant of 0.030 nM whereas the remaining sites had a low affinity dissociation constant of 0.64 nM. Apomorphine (1.0 μM) enhanced the binding of [3H](-)QNB by an apparent conversion of low to high affinity sites. A variety of other agents were screened for their ability to enhance [3H](-)QNB binding, and a pattern generally consistent with a dopaminergic effect was observed although some evidence for a β-adrenergic effect was demonstrable. The potent neuroleptics haloperidol, spiperone and sulpiride failed to antagonize the apomorphine enhancement of [3H](-)QNB binding as well as some adrenergic antagonists. However, the potent inhibitors of the dopamine-sensitive adenylate cyclase, α-flupenthixol and fluphenazine, specifically blocked the apomorphine enhancement of [3H](-)QNB binding with Ki values of approximately 0.1 μM.
UR - http://www.scopus.com/inward/record.url?scp=0019861982&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0019861982&partnerID=8YFLogxK
U2 - 10.1016/0024-3205(81)90512-9
DO - 10.1016/0024-3205(81)90512-9
M3 - Article
C2 - 7253832
AN - SCOPUS:0019861982
SN - 0024-3205
VL - 28
SP - 2441
EP - 2448
JO - Life Sciences
JF - Life Sciences
IS - 21
ER -