Evaluation of quaternized and neutral muscarinic receptor ligands in normal and DES-treated rat.
The localization of quaternized muscarinic receptor (mAChR) antagonists, [11C]methyl tropanyl benzilate ([11C]MTRB) and [11C]methyl quinuclidinyl benzilate ([11C]MQNB), in rat pituitary was compared to that of [11C]tropanyl benzilate ([11C]TRB), a neutral antagonist. The quaternized ligands localize via a mAChR-mediated mechanism as shown by 60% reduction in radioactivity concentrations in the presence of QNB. [11C]TRB appears to localize primarily by a non-mAChR specific mechanism. Induction of pituitary prolactinomas by diethylstilbestrol resulted in a reduction of [11C]MTRB pituitary localization compared to normals. Elevated serum prolactin levels due to prolactinoma presence had no measurable effect on myocardial [11C]MTRB uptake or on KD values. Bmax values for myocardial mAChR were similar for controls and for DES exposure of 10 weeks.
Otto
C A
CA
University of Michigan-Dearborn, 48128.
Mulholland
G K
GK
DeMattos
S B
SB
Sherman
P S
PS
Pisani
T L
TL
Hingorani
G
G
D000818:Animals; D001921:Brain / Q000378:metabolism; D004054:Diethylstilbestrol / Q000494:pharmacology*; D005069:Evaluation Studies as Topic; D005260:Female; D008024:Ligands; D009206:Myocardium / Q000378:metabolism; D010277:Parasympathomimetics; D010902:Pituitary Gland / Q000378:metabolism; D011813:Quinuclidinyl Benzilate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011976:Receptors, Muscarinic / Q000187:drug effects*; D014018:Tissue Distribution; D014326:Tropanes / Q000493:pharmacokinetics
D008024:Ligands; D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; D014326:Tropanes; C071352:N-methyltropanyl benzilate; C071351:tropanyl benzylate; D011813:Quinuclidinyl Benzilate; D004054:Diethylstilbestrol; C054940:clidinium