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

sigma 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 sigma 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 sigma receptor ligands are mediated via two receptor subtypes, one stimulatory and the other inhibitory, and only the inhibitory subtype is subject to desensitization.