Apparent desensitization of a σ receptor sub-population in neonatal rat cardiac myocytes by pre-treatment with σ receptor ligands

σ Receptor ligands induce marked effects on contractility in cardiac myocytes from neonatal and adult rats (Ela et al., 1994, J. Pharmacol. Exp. Ther. 269, 1300-1309; Novakova et al., 1995, Eur. J. Pharmacol. 286, 19-30). Augmentation or attenuation of the contractile amplitude was observed under different experimental conditions. Preincubation of neonatal cardiomyocytes with a σ receptor ligand ((+)-(3-hydroxyphenyl)-N-(1-propyl)-piperidine ((+)-3PPP), (+)-pentazocine, or haloperidol) changed the response to re-application of the ligand after cell wash. The inhibitory effect was abolished, while the stimulatory effect became much more pronounced. We suggest that the effects of σ receptor ligands are mediated via two receptor subtypes, one stimulatory and the other inhibitory, and only the inhibitory subtype is subject to desensitization.