Comparison of two different arterial tissues suggests possible 5-hydroxytryptamine2 receptor heterogeneity.
A comparison of activities and affinities of several known and novel compounds in the isolated rat thoracic aorta (RA) and the rabbit femoral artery (RFA) was undertaken to evaluate these two tissues for use in screening for functional 5-hydroxytryptamine2 (5-HT2) receptor activity. Affinities for 5-HT and for ketanserin against 5-HT-elicited contractions in both vascular tissues suggested the presence of homogeneous 5-HT2 receptors with values consistent with other reported 5-HT2 receptor preparations. However, further studies showed compounds which exhibited either partial agonism in the RFA and competitive antagonism of 5-HT in the RA, or antagonism of 5-HT in both arteries with different affinities. Affinity constants calculated from the isolated vascular tissue studies were compared with affinity constants calculated for inhibition of [3H]ketanserin binding in the frontal cortices of both the rat and the rabbit. There were no significant differences between the pKi values in the rat and the rabbit cortical membranes or between these pKi's in either species and the pA2 values in the RA. Several of the affinities for both the partial agonists and the antagonists in the RFA were significantly different from the binding pKi and the pA2 values in the RA. These findings suggest identity between the [3H]ketanserin binding site in the cortices of both species and the 5-HT2 receptor in the RA; however, the contractile 5-HT receptor in the RFA, although showing some characteristics of a 5-HT2 receptor, is significantly different. We suggest that there may be functional subtypes of the vascular 5-HT receptor.
Killam
A L
AL
Department of Pharmacology, University of Arizona, Tucson.
Nikam
S S
SS
Lambert
G M
GM
Martin
A R
AR
Nelson
D L
DL
D000818:Animals; D001013:Aorta, Thoracic; D001665:Binding Sites; D005263:Femoral Artery; D007650:Ketanserin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D007650:Ketanserin