5-Hydroxytryptamine receptor in rabbit aorta: characterization by butyrophenone analogs

Area of Science:

• Pharmacology
• Neuroscience
• Cardiovascular Research

Background:

• 5-hydroxytryptamine (5-HT) plays a role in vascular contraction.
• Butyrophenone analogs are known to interact with various receptors.

Purpose of the Study:

• To investigate the antagonistic effects of spiperone and related butyrophenones on 5-HT-induced contractions in rabbit aorta.
• To explore the relationship between aortic receptors and brain 5-HT2 binding sites.

Main Methods:

• Isolated rabbit aorta rings were used to measure contractile responses.
• Competitive antagonism assays were performed with spiperone and four analogs.
• Binding affinities (Kd) for [3H]ketanserin and [3H]spiperone in rat brain membranes were compared to aortic inhibition constants (Kb).

Main Results:

• Spiperone and four butyrophenone analogs competitively antagonized 5-HT-induced contractions with nanomolar Kb values.
• The rank order of antagonism was spiperone > spirilene > benperidol > azaperone > haloperidol.
• Aortic receptor inhibition constants (Kb) closely matched brain receptor binding affinities (Kd), suggesting congruence between aortic "D" receptors and brain 5-HT2 sites.

Conclusions:

• Aortic "D" receptors likely correspond to 5-HT2 type binding sites found in the rat brain.
• The non-butyrophenone portion of the antagonist molecules significantly influences their potency in antagonizing 5-HT receptors in the aorta.