α-Adrenoceptor Agonists Produce Ca²⁺ Oscillations in Isolated Rat Aorta : Role of Protein Kinase C

Abstract

We investigated the relationship between tension development and the cytosolic free Ca²⁺ level ([Ca²⁺]₁) in responses to norepinephrine (NE) and selective α₂-adrenoceptor agonist, UK14, 304 of the endothelium-denuded rat aorta loaded with fura PE-3. NE (3×10^-8 M) evoked a rapid increase in [Ca²⁺]₁ followed by slight decreasing to a steady state level and produced a contraction. After the NE-induced increase in [Ca²⁺]₁ had reached a maximum, the [Ca²⁺]₁ showed persistent oscillations. The Ca²⁺ oscillations were super-imposed on the sustained increase in [Ca²⁺]₁ . UK14, 304 (3×10^-6 M) also evoked an increase in [Ca²⁺]₁ and produced a contraction. However, the UK14, 304-induced effect on [Ca²⁺]₁ was characterized by pronounced oscillations, and the amplitude of the sustained increase in [Ca²⁺]₁ was less than that seen with NE. Protein kinase C inhibitor, Ro31-8220 (3×10^-6 M) and verapamil (10^-5 M) abolished both NE- and UK14, 304-evoked Ca²⁺ oscillations. UK14, 304-induced contractions were also strongly inhibited by Ro31-8220 and verapamil. However, NE-induced contractions were partly inhibited by these inhibitors. The sustained increases in [Ca²⁺]₁ evoked NE and UK14, 304 were not significantly inhibited by Ro31-8220 and verapamil. These results suggest that NE and UK14, 304 produce Ca²⁺ oscillations during sustained contractions in rat aorta. The α₂-adrenoceptor agonist, UK14, 304-induced sustained contraction and Ca²⁺ oscillations may be due to PKC activation and opening of voltage-dependent L-type Ca²⁺ channels.