A 5-HT4-like receptor in human right atrium

Area of Science:

• Pharmacology
• Cardiovascular Physiology
• Neuroscience

Background:

• Serotonin (5-hydroxytryptamine, 5-HT) plays a role in cardiovascular function.
• Gastrokinetic benzamides like renzapride and cisapride interact with 5-HT receptors.
• Understanding 5-HT receptor subtypes in the human heart is crucial for drug development.

Purpose of the Study:

• To investigate the effects of 5-carboxamidotryptamine (5-CT), renzapride, and cisapride on human right atrial contractile force and cyclic AMP (cAMP) levels.
• To compare these effects with 5-HT.
• To characterize the 5-HT receptor subtype involved in the human right atrium.

Main Methods:

• Isolated human right atrial appendages from patients undergoing open heart surgery were used.
• Contractile force and cAMP levels were measured in response to various drugs.
• Receptor pharmacology was assessed using selective antagonists and by comparing agonist potencies.

Main Results:

• 5-HT, 5-CT, renzapride, and cisapride all increased contractile force, with potency order: 5-HT > renzapride > cisapride > 5-CT.
• Renzapride and cisapride acted as partial agonists.
• ICS 205-930 blocked the effects, indicating involvement of 5-HT4 receptors.
• 5-HT, 5-CT, and renzapride increased cAMP levels, with 5-HT and renzapride also increasing protein kinase activity.

Conclusions:

• A human right atrial 5-HT receptor, designated 5-HT4-like, was identified.
• This receptor shares similarities with 5-HT4 receptors in other species but exhibits differences in benzamide potency and efficacy.
• The findings suggest a role for 5-HT4-like receptors in regulating human atrial function and highlight potential drug interactions.