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.
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Wright et al. (1989) studied this question.