The enigma of renin and 5-HT_1A agonists

Typically, injection of 5-HT_1A agonists to adult rats does not increase the secretion of renin. However, inhibition of 5-HT_1A receptors with the antagonist WAY100635 exposes a stimulatory effect of 8-OH-DPAT. Similarly, desensitization ol 5-HT_1A receptors by chronic administration of 5-HT uptake blockers (fluoxetine or paroxetine) exposes a stimulatory effect of 8-OH-DPAT or ipsapirone on the release of renin (Li et al., Biol. Psychiatry 1994; Brain Res. 1993). These observations suggest that the effects of these 5-HT_1A agonists on the secretion of renin are not mediated bv activation of 5-HT_1A receptors. To examine whether monoamine receptors mediate the effect of 8-OH-DPAT on renin release, rats were pretreated with the irreversible monoamine antagonist EEDQ (10 mg/kg se) and were subsequently (24 hr later) challenged with 8-OH-DPAT (500 μg/kg, sc). This dose of EEDQ reduces ³H-8-OH-DPAT binding by ± 70%. The effectiveness of EEDQ was verified from its ability to completely block the oxytocin response to 8-OH-DPAT. In vehicle pretreated rats. 8-OH-DPAT did not increase plasma renin activity or concentration. However, in EEDQ pretreated rats. 8-OH-DPAT produced a significant (4-6 fold) increase in both plasma renin activity and plasma renin concentration. Since EEDQ inactivates 5-HT_1A and most other monoamine receptors, these results suggest that a non-monoamine receptor may mediate the effect of 8-OH-DPAT on the secretion of renin.