INOTROPIC ACTION OF SIGMA-RECEPTOR LIGANDS IN ISOLATED CARDIAC MYOCYTES FROM ADULT-RATS

High affinity binding sites for a receptor ligands were found in membr anes of cardiac myocytes from adult rats. The sigma receptor ligand ()-3-hydroxyphenyl-N-(1-propyl)piperidine ((+)-3-PPP) binds with a K-d of 17.9 +/- 4.0 nM and a B-max of 275 +/- 32.1 fmol/mg protein. Compet ition experiments of (+)-pentazocine with [H-3]1,3-di-O-tolylguanidine ([H-3]DTG) binding yielded a K-i of 6.1 +/- 1.3 nM. The majority of t he sites (> 80%) were of the sigma(1) subtype. Exposure of isolated ca rdiomyocytes from adult rats to (+)-3-PPP (10 nM-1.0 mu M) caused a ma rked concentration-dependent increase in the amplitude of systolic cel l contraction, reaching 149% of control level, with an apparent ED(50) value of 4.5 nM. The increase in the contraction amplitude was marked ly inhibited by pretreatment with verapamil or thapsigargin. An increa se in the amplitude of [Ca2+](i) transients, similar to that in the am plitude of cell contraction, was observed in indo-1-loaded cardiomyocy tes exposed to 0.1 mu M (+)-3-PPP. Exposure to 10 nM of haloperidol or (+)-pentazocine induced an increase in the amplitude of contraction, reaching 188% and 138% (respectively) of control level. A lower concen tration of haloperidol or (+)-pentazocine (1 nM) did not induce an inc rease in the contraction amplitude but rather reduced the amplitude to 70-80% of control.