Background Decreased myocardial adenylate cyclase activity in response
to guanine nucleotide stimulation has been recently demonstrated in d
enervated myocardium of transplant patients, suggesting that changes i
n left ventricular muscarinic receptors may occur. Methods and Results
The concentration and affinity constants of myocardial muscarinic rec
eptors were determined by positron emission tomography with C-11-label
ed methylquinuclidinyl benzilate (MQNB), a specific hydrophilic antago
nist, in six transplant patients 4.7+/-2.3 months after surgery and in
six normal subjects. Patients had no sign of cardiac rejection at end
omyocardial biopsy. After intravenous injections of MQNB, time-activit
y curves were obtained over different regions of interest and were fit
ted to a nonlinear mathematical model. No difference in the concentrat
ion of muscarinic receptors was found in transplant patients compared
with control subjects: 24+/-4 versus 26+/-7 pmol/mL tissue, respective
ly (P=NS). The association rate constant k(+1), the dissociation rate
constant k(-1), and thus the equilibrium-dissociation constant Kd were
the same in transplant patients compared with control subjects. Concl
usions Despite known decreased GTP-stimulated adenylate cyclase activi
ty in transplant patients, the density and affinity constants of myoca
rdial muscarinic receptors are not altered. This suggests abnormalitie
s of the signal-transduction function, such as a change in the guanine
nucleotide binding proteins.