Alpha-adrenoceptor agonists produce Ca2+ oscillations in isolated rat aorta: role of protein kinase C.
We investigated the relationship between tension development and the cytosolic free Ca2+ level ([Ca2+]i) in responses to norepinephrine (NE) and selective alpha2-adrenoceptor agonist, UK14,304 of the endothelium-denuded rat aorta loaded with fura PE-3. NE (3 x 10(-8) M) evoked a rapid increase in [Ca2+]i followed by slight decreasing to a steady state level and produced a contraction. After the NE-induced increase in [Ca2+]i had reached a maximum, the [Ca2+]i showed persistent oscillations. The Ca2+ oscillations were superimposed on the sustained increase in [Ca2+]i. UK14,304 (3 x 10(-6) M) also evoked an increase in [Ca2+]i and produced a contraction. However, the UK14,304-induced effect on [Ca2+]i was characterized by pronounced oscillations, and the amplitude of the sustained increase in [Ca2+]i was less than that seen with NE. Protein kinase C inhibitor, Ro31-8220 (3 x 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+]i 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 alpha2 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.
Suenaga
H
H
Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Tokyo, Japan.
Kamata
K
K
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology*; D000068438:Brimonidine Tartrate; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects*; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000201:enzymology; D009638:Norepinephrine / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D007211:Indoles; D011810:Quinoxalines; D000068438:Brimonidine Tartrate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D014700:Verapamil; D011493:Protein Kinase C; C064758:Ro 31-8220; D009638:Norepinephrine