(S)-reticuline induces vasorelaxation through the blockade of L-type Ca(2+) channels.
In Brazil, various species of the genus Ocotea are used in folk medicine for treating several diseases. The chemical characterization of this plant showed the presence of alkaloids belonging to the benzyltetrahydroisoquinoline family, the major component of which is (S)-reticuline. The present study investigated whether (S)-reticuline exerts an inhibitory effect on smooth muscle L-type Ca(2+) channels. Tension measurements and patch clamp techniques were utilized to study the effects of (S)-reticuline. Whole-cell Ca(2+) currents were measured using the A7r5 smooth muscle cell line. (S)-reticuline antagonized CaCl(2)- and KCl-induced contractions and elicited vasorelaxation. It also reduced the voltage-activated peak amplitude of I (Ca,L) in a concentration-dependent manner. (S)-reticuline did not change the characteristics of current density vs. voltage relationship. (S)-reticuline shifted leftwards the steady-state inactivation curve of I (Ca,L). The application of dibutyryl cyclic adenosine monophosphate to the cell decreased the amplitude of Ca(2+) currents. In cells pretreated with forskolin, an adenylate cyclase activator, the addition of (S)-reticuline caused further inhibition of the Ca(2+) currents suggesting an additive effect. The results obtained show that (S)-reticuline elicits vasorelaxation probably due to the blockade of the L-type voltage-dependent Ca(2+) current in rat aorta. The reported effect may contribute to the potential cardioprotective efficacy of (S)-reticuline.
Medeiros
Marcos Antônio A
MA
Laboratory of Pharmaceutical Technology (LTF), Universidade Federal da Paraíba, João Pessoa, PB, Brazil.
Nunes
Xirley P
XP
Barbosa-Filho
José M
JM
Lemos
Virginia S
VS
Pinho
José F
JF
Roman-Campos
Danilo
D
de Medeiros
Isac A
IA
Araújo
Demetrius Antonio M
DA
Cruz
Jader S
JS
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D044182:Benzylisoquinolines / Q000737:chemistry / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000502:physiology*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D004789:Enzyme Activation; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D027444:Ocotea; D018408:Patch-Clamp Techniques; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D014664:Vasodilation / Q000187:drug effects*
D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D010936:Plant Extracts; D005576:Colforsin; D003994:Bucladesine; D000262:Adenylyl Cyclases; C003298:reticuline