Effects of a Labdane Diterpene Isolated from Brickellia paniculata on Intracellular Ca²⁺ Deposit of Guinea-Pig Ileal Longitudinal Muscle

Introduction

Brickellia paniculata (Asteraceae) is a medicinal plant commonly used in Southeastern Mexico to treat colics, abdominal pains and watery diarrhoea [1], [2]. In a previous study, from the methanolic extract were isolated a flavonoid (xanthomicrol) and a labdane diterpene, this latter compound was structurally characterized as 3α-angeloyloxy-2α-hydroxy-13,14Z-dehydrocativic acid (AAHDD) [3]. The structures have already been reported and their identity was confirmed by comparison with published physical and spectroscopic data [4], [5], [6]. Both compounds relaxed the segments of isolated guinea-pig ileum stimulated with high K⁺ and the effect was correlated with an interference of Ca²⁺ mobilization in the cell. Furthermore, a competitive calcium-antagonistic activity was described for AAHDD, although the precise mechanism underlying this effect was not demonstrated. It is well documented that in the guinea pig ileum, K⁺ depolarization induces the opening of the voltage-dependent calcium channels increasing the influx of Ca²⁺ into the cell; as a response to the rise of free Ca²⁺ in the cytosol, the muscle contracts. Calcium entry is the primary but not the sole mechanism of increasing [Ca²⁺]i, since the release of the cation from intracellular deposits can also occur. Phasic response to K⁺ has been attributed to a rise in cytosolic free Ca²⁺ which is released from intracellular stores. On the other hand, the tonic component has been associated with the opening of the voltage-dependent calcium channels causing Ca²⁺ influx to increase [7], [8], [9].

As has been observed, the compound AAHDD inhibited with the same potency the K⁺ evoked phasic and tonic components of the contractile response. This work was undertaken to gain further information about a possible blocking action of AAHDD at intracellular Ca²⁺ stores.[]

References

• 1 Berlin E A, Berlin B. Medical Ethnobiology of the Highland Maya of Chiapas. Mexico; The Gastrointestinal Diseases. Princeton Academic Press. USA 1995: 126, 451
• 2 Berlin B, Berlin E A, Meckes M, Lozoya X, Villarreal M L, Tortoriello J. The scientific basis of gastrointestinal herbal medicine among the highland Maya of Chiapas. Mexico; In: Naked Science Anthropological Inquiry into Boudaries, Power and Knowledge. Nader L, editor Routledge. USA 1996: 43-68
• 3 Meckes M, Calzada F, Paz D, Rodríguez J. Effects of active compounds isolated from Brickellia paniculata on isolated smooth muscle. 38th Annual Meeting of the American Society of Pharmacognosy Iowa. U.S.A; 1997
• 4 Stout G, Falk-Stout V. The structure and synthesis of xanthomicrol.  Tetrahedron. 1961;  14 296-303
• 5 Bohlmann F, Bapuji M, Jakupovic J, King R, Robinson H. Unusual diterpenes from Brickellia eupatoriedes .  Phytochemistry. 1982;  21 181-6
• 6 Bohlmann F, Zdero C h. Naturally occurring terpene derivatives. Constituents of the genus Brickellia .  Chem Ber. 1976;  109 1436-45
• 7 Nasu T, Oosako H, Shibata H. Dantrolene blocks the tonic contraction and calcium influx evoked by K⁺ in ileal longitudinal smooth muscle.  Gen Pharmacol. 1996;  27 513-7
• 8 Dessy C h, Godfried T. The effect of L-type calcium channel modulators on the mobilization of intracellular calcium stores in guinea-pig intestinal smooth muscle.  Br J Pharmacol. 1996;  119 142-8
• 9 Urakawa N, Holland W C. ⁴⁵Ca uptake and tissue calcium on K-induced phasic and tonic contraction; Am.  J.. Physiol.1964;  207 873-6
• 10 Honda K, Takano Y, Kamiya H. Involvement of protein kinase C in muscarinic agonist-induced contractions of guinea-pig ileal longitudinal muscle.  Gen Pharmacol. 1996;  27 957-61
• 11 Himpens B, Somlyo A P. Free-calcium and force transients during depolarization and pharmacomechanical coupling in guinea-pig smooth muscle.  J Physiol. 1988;  395 507-30
• 12 Usune S, Katsuragi T, Furukawa T. Discrimination by nimodipine, but not by nifedipine, between phasic and tonic contractions of guinea-pig taenia coli induced by K⁺ depolarization.  Can J Physiol Pharmacol. 1996;  73 1600-4
• 13 Okamoto H, Inoue K, Kamisaki T, Takahashi K, Sato M. Regional differences in calcium sensitivity in the guinea-pig intestine.  J Pharm Pharmacol. 1997;  49 981-4
• 14 Uyama Y, Imaizumi Y, Watanabe M B. Cyclopiazonic acid, an inhibitor of Ca²⁺-ATPase in sarcoplasmic reticulum increases excitability in ileal smooth muscle.  Brit J Pharmacol. 1993;  110 565-72
• 15 Hwang K S, Van Breemen C. Ryanodine modulation of ⁴⁵Ca²⁺ efflux and tension in rabbit aortic smooth muscle.  Pflüg Arch _Eur J Physiol. 1987;  408 343-50
• 16 Iino M, Kobayashi T, Endo M. Use of ryanodine for functional removal of the calcium store in smooth muscle cells of the guinea-pig.  Biochem Biophys Res Comm. 1988;  152 417-22
• 17 Putney JW J r, Bird G SJ. The signal for capacitative calcium entry.  Cell . 1993;  75 199-201