The selective "5-HT1-like" receptor agonist
5-carboxamidotryptamine (5-CT, 0.2-1.6 micrograms/kg bolus i.v.),
serotonin (5-HT, 3-10 micrograms/kg), and
phenylbiguanide (10-40 micrograms/kg) all elicited the "Bezold-Jarisch-like"
bradycardia reflex in conscious rabbits. This reflex was antagonised by the
5-HT3 receptor antagonist,
MDL 72222. After autonomic blockade (
mecamylamine), 5-CT and
5-HT infusion (i.v.) caused renal artery
spasm (Doppler
flowmeter) that was antagonised by
ketanserin, a 5-HT2-receptor antagonist. Both 5-CT and
5-HT caused 5-HT1-like receptor mediated increases in hindquarter conductance that were unaltered by
ketanserin (0.5 mg/kg). The anomalous 5-HT3 and 5-HT2 receptor actions of 5-CT were completely prevented by 16 h pretreatment with
reserpine (5 mg/kg) that lowered total serum
serotonin to less than 3% of normal but did not reduce the cardiovascular actions of
5-HT.
Fluoxetine (1 mg/kg i.v.), an inhibitor of
5-HT uptake into platelets, significantly attenuated the Bezold-Jarisch-like reflex evoked by 5-CT but not by
5-HT. These studies suggest that 5-CT is carried into platelets where it releases
5-HT. This illustrates how apparent receptor selectivity asserted in in vitro assays can be destroyed in vivo.