Publication details
Desensitisation of Sigma Receptors in Guinea Pig Atria
| Authors | |
|---|---|
| Year of publication | 2003 |
| Type | Article in Proceedings |
| Conference | 79. Fyziologické dny, Sborník abstraktů |
| MU Faculty or unit | |
| Citation | |
| Field | Physiology |
| Keywords | guinea pig heart; cardiac sigma receptor; desensitisation; haloperidol; mechanical restitution |
| Description | Previous studies have shown a modulatory effect of sigma receptor activation on cardiac contractility and its desensitisation in rat myocardium. This study was aimed at verifying the effects of sigma ligands in a more typical model, i.e. guinea pig atria. Left atriafrom 19 adult male guinea pigs were placed in horizontal perfusion bath (30C) with aerated Krebs-Henseleit solution (1.25 mM Ca2+). The stimulation rate was 1Hz. Contractions were recorded isometrically. After 30-45 minutes of stabilisation, sigma ligand haloperidol in 10nM concentration was administered for 30 minutes. Then, a period of 15 min washout and another 30 min period of haloperidol perfusion followed. The changes of amplitude of contraction and of mechanical restitution were investigated. In all cases, marked positive inotropic effect was observed (increase in the amplitude ranging from 36 to 123%, with maximal effect in the 5th minute of perfusion). The mechanical restitution pattern under the effect of sigma receptor ligand was not altered. This positive inotropic effect was attenuated after the second haloperidol administration (an increase in the amplitude ranging from 9 to 93%, with the maximum effect in the 3rd minute). In conclusion: the positive inotropic effect of haloperidol, previously described in rat myocardium, was confirmed also in guinea pig atrial preparations. Its attenuation after the repeated exposure indicates that sigma receptors in guinea pig heart undergo a desensitisation process previously reported in rat myocardium. According to the effect of haloperidol on the mechanical restitution it is possible to speculate that it is mediated via increased availability of cytoplasmatic calcium. |