[3H]5-hydroxytryptamine uptake and release in cat cerebral arteries

Area of Science:

• Neuropharmacology
• Vascular Physiology

Background:

• Serotonin (5-HT) plays a crucial role in regulating vascular tone.
• Understanding the mechanisms of 5-HT release and storage in cerebral arteries is vital for cardiovascular health.

Purpose of the Study:

• To investigate the mechanisms of [3H]serotonin (5-HT) release from cat cerebral arteries.
• To elucidate the role of adrenergic nerve endings and specific receptors in 5-HT release.

Main Methods:

• Electrical field stimulation of cat cerebral arteries preincubated with [3H]serotonin (5-HT).
• Pharmacological manipulation using tetrodotoxin, B-HT 920, phentolamine, phorbol 12,13-dibutyrate, cocaine, and ouabain.
• Denervation using 6-hydroxydopamine (6-OHDA) to assess the role of adrenergic nerves.
• Measurement of [3H]5-HT uptake and 5-HT-mediated potentiation of noradrenaline (NA) contractions.

Main Results:

• Electrical stimulation induced [3H]5-HT release, sensitive to tetrodotoxin, alpha 2-adrenoceptor blockade (phentolamine), and protein kinase C activation (phorbol 12,13-dibutyrate).
• Release was reduced by alpha 2-adrenoceptor agonism (B-HT 920), calcium removal, and 6-OHDA denervation.
• [3H]5-HT uptake was significantly decreased by cocaine, ouabain, and 6-OHDA denervation, indicating accumulation in adrenergic nerve endings.
• 5-HT did not potentiate noradrenaline-induced contractions.

Conclusions:

• Serotonin (5-HT) is primarily stored within perivascular adrenergic nerve endings in cat cerebral arteries.
• Presynaptic alpha 2-adrenoceptors and protein kinase C modulate 5-HT release.
• 5-HT does not appear to amplify noradrenaline responses in these arteries.