Three distinct subtypes of serotonergic receptors mediate the triphasic blood pressure response to serotonin in rats

In pentobarbitone- or urethane-anaesthetized normotensive rats the triphasic pressure response to serotonin (5-HT): a short-lasting depressor phase with an intense bradycardia, a pressor phase and a prolonged hypotension, was investigated. The highly selective 5-HTM antagonist ICS 205-930 (1 microgram/kg) inhibited the first but not the second or third phase. The 5-HT2 antagonist ketanserin (0.1 mg/kg) inhibited the second but not the first or third phase. Following selective blockade of the pressor component with ketanserin (0.1 mg/kg), the hypotensive potency of eight serotonin receptor agonists was quantified (-log ED50). A correlation (r = 0.75, P less than 0.05) was observed between this parameter and the displacement of the 5-HT1 ligand [3H]-5-HT. It is suggested that the three phases are due to 5-HTM-, 5-HT2- and 5-HT1-receptor activation, respectively.