Presynaptic dopamine receptors in the cardiovascular system

Area of Science:

• Neuropharmacology
• Cardiovascular Physiology

Background:

• Presynaptic dopamine receptors on sympathetic neurons inhibit norepinephrine release.
• These receptors are primarily of the DA-2 subtype.
• DA-2 receptor agonists have potential antihypertensive and bradycardic effects.

Purpose of the Study:

• To investigate the role of peripheral presynaptic DA-2 receptors in the context of monoamine oxidase inhibitor (MAOI) treatment.
• To determine if blocking DA-2 receptors affects norepinephrine release following chronic MAOI administration.

Main Methods:

• Electrically-evoked release of 3H-norepinephrine was measured from perfused atrial slices of cats.
• Cats were chronically treated with the MAOI pargyline.
• The effect of the selective DA-2 antagonist S-sulpiride on norepinephrine release was assessed under control and pargyline-treated conditions.

Main Results:

• S-sulpiride alone did not enhance norepinephrine release in control conditions.
• Following chronic pargyline treatment, S-sulpiride administration resulted in a significant increase in electrically-evoked 3H-norepinephrine release.
• This suggests that DA-2 receptors normally restrain norepinephrine release, and this restraint is altered after MAOI treatment.

Conclusions:

• Peripheral presynaptic DA-2 receptors are involved in modulating norepinephrine release.
• The findings suggest a potential role for these receptors in the antihypertensive mechanisms of MAOIs.
• Further research is warranted to elucidate the precise contribution of peripheral DA-2 receptors to MAOI-induced hypotension.