Pharmacological Studies of Lycorenine, an Alkaloid of Lycoris Radiata Herb.: II. Effects of Blood Pressure in Rats and Dogs and the Mechanism of Tachyphylaxis to the Vasodepressor Action of Lycorenine in Rats

Abstract

Abstract-Effects of nonspecific smooth muscle relaxants, papaverine (10-' M) and Aspaminol (I,1-diphenyl-3-piperidinobutanol hydrochloride, 10-' M), and Ca-blocker, D-600 (10-6 M) on Ca-release and Ca-binding in the microsomal fractions of rabbit taenia coli were determined.The doses necessary to relax the K-depolarized taenia coli maximally were used. Ca-binding in the microsomal fractions was inhibited by Aspaminol and D-600 and increased by papaverine in the concentration used. On the other hand, Ca-release from the Ca-incorporated microsomal fractions was inhibited by papaverine and Aspaminol but was not influenced by D-600. Changes observed in Ca-transfer may be related to relaxation of smooth muscle induced by the test drugs.It was reported that nonspecific smooth muscle relaxants, papaverine and Aspaminol, and Ca-blockers inhibited the responses of K-depolarized intestinal smooth muscle to CaCl2 and also decreased Ca-uptake by the depolarized intestinal smooth muscle from the bath fluid (1). Since papaverine is a potent inhibitor of cyclic AMP-phosphodiesterase (2), relaxation of smooth muscle is considered to be partly due to an increase of intracellular levels of cyclic AMP. However, Aspaminol and Ca-blockers are found to have little in hibitory action on phosphodiesterase activity (3, 4). Nonspecific inhibitory action of Aspaminol (5, 6) and of Ca-blockers (7) can be decreased to a great extent by increasing the Ca-concentration in the bath fluid, while that of papaverine is only slightly increased. As little is known of the differences in the effects of the smooth muscle relaxants and Ca-blockers on Ca-release and Ca-binding in the microsomal fractions from the intestinal smooth muscle and of differences in changes in Ca-transfer induced by the nonspecific smooth muscle relaxants and Ca-blockers, we carried out studies in an attempt at elucidation. MATERIALS AND METHODSA piece (3 to 4 cm) of the taenia coli isolated from male rabbits, weighing 2 to 3 kg, was suspended in a 20 ml organ bath filled with a KCl-solution kept at 32'C and gassed with a mixture of 95% 02 and 5 % C02. Responses to drugs were recorded isotonically.The KCI-solution used had the following composition (mM) : KCl 159.6, CaCl2 2.2, MgCl2 2.1, NaHCO3 5.9 and glucose 2.8.Estimation of Ca-binding in the microsomal fractions was carried out by the method of Carsten (8)

Ketamine‐inhibition of calcium‐induced contractions in depolarized rat uterus: a comparison with other calcium antagonists

“…The relaxant effects of papaverine and theophylline may involve additional mechanisms. These drugs increase the efflux and uptake of Ca2" by intracellular organelles (Thorens & Haeusler, 1979;Takayanagi et al, 1980;Imai & Kitagawa, 1981;Koike & Takayanagi, 1981;Huddart et al, 1983;Qashi & Takayanagi, 1983) and also inhibit adenosine 3':5'-cyclic monophosphate (cyclic AMP) phosphodiesterase (Weiss & Hait, 1977;Mukai et al, 1981). Furthermore, recent evidence indicates that most of the calcium entry blockers have an additional intracellular site ofaction, related to an increase of Ca2" efflux or to stimulation of Ca2" uptake (Spedding, 1983;Saida & Van Breemen, 1983;Cohen et al, 1984).…”

Effects of Papaverine, Benactyzine and D600 on Ca2+ efflux, determined by means of a Ca2+-selective electrode, from guinea pig taenia coli into a Ca2+-free physiological solution.

“…1, A). This might be related to the stimulatory effect of papaverine on Ca uptake by microsomal fraction (6) and/or mitochondrial fraction (26) of smooth muscles and to the inhibitory effect of papaverine on Ca release by microsomal fraction (27).…”

Effect of 1,1-diphenyl-3-piperidinobutanol hydrochloride (aspaminol) on the stimuli-induced calcium uptake in rat brain synaptosomes.

“…Verapamil and D 600 which have been shown to prevent the influx of calcium in the smooth muscle (13) and its microsomal fractions (14) inhibited the potassium stimulated calcium uptake in rat brain synaptosomes (11)(12). Aspaminol (1,1 diphenyl-3 piperidinobutanol hydrochloride), a nonspecific smooth muscle relaxant, also inhibited the calcium uptake in the smooth muscle (15) and its microsomal fractions (14,16).…”

“…Aspaminol (1,1 diphenyl-3 piperidinobutanol hydrochloride), a nonspecific smooth muscle relaxant, also inhibited the calcium uptake in the smooth muscle (15) and its microsomal fractions (14,16). Therefore, we attempted to determine whether or not Aspaminol also would inhibit the calcium uptake in rat brain synaptosomes.…”

“…Nachshen and Braustein (11) and lchida et al (12) showed that verapamil and D 600 inhibited the calcium uptake in the syn aptosomes from rat brain. Verapamil and D 600 also inhibited the calcium uptake in smooth muscle (13) and in microsomal fractions (14). Takayanagi et al found that 1,1-diphenyl-3-piperidinobutanol hydro chloride (Aspaminol), a nonspecific smooth muscle relaxant, also inhibited the calcium uptake in smooth muscle (15) and in micro somal fractions (14,16).…”