5-carboxamidotryptamine elicits 5-HT2 and 5-HT3 receptor-mediated cardiovascular responses in the conscious rabbit: evidence for 5-HT release from platelets.
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.
Wright
C E
CE
Baker Medical Research Institute, Prahran, Victoria, Australia.
Angus
J A
JA
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D006614:Hindlimb / Q000098:blood supply; D008297:Male; D011817:Rabbits; D011985:Receptors, Serotonin / Q000187:drug effects*; D012018:Reflex / Q000187:drug effects*; D012077:Renal Artery / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology; D012701:Serotonin / Q000031:analogs & derivatives* / Q000097:blood* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D005473:Fluoxetine; D012701:Serotonin; D012110:Reserpine; C047087:5-carboxamidotryptamine