Inotropic action of σ receptor ligands in isolated cardiac myocytes from adult rats

High affinity binding sites for σ receptor ligands were found in membranes of cardiac myocytes from adult rats. The σ 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. Competition experiments of (+)-pentazocine with [³H]1,3-di-O-tolylguanidine ([³H]DTG) binding yielded a K_i of 6.1 ± 1.3 nM. The majority of the sites (> 80%) were of the σ₁ subtype. Exposure of isolated cardiomyocytes from adult rats to (+)-3-PPP (10 nM-1.0 μM) caused a marked concentration-dependent increase in the amplitude of systolic cell contraction, reaching 149% of control level, with an apparent ED₅₀ value of 4.5 nM. The increase in the contraction amplitude was markedly inhibited by pretreatment with verapamil or thapsigargin. An increase in the amplitude of [Ca²⁺]_i transients, similar to that in the amplitude of cell contraction, was observed in indo-1-loaded cardiomyocytes exposed to 0.1 μM (+)-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 concentration of haloperidol or (+)-pentazocine (1 nM) did not induce an increase in the contraction amplitude but rather reduced the amplitude to 70-80% of control.