Effects of synthetic CU 18-08, CU18-10 and CU 18-11 compounds on Ca[superscript 2+] mobilization in smooth muscle of isolated rat arota

Abstract

It has been shown that CU 18-08, CU 18-10, acyl aniline derivatives as well as CU 18-11, an acyl aminopyridine derivative suppressed the spontaneous contraction of rat duodenum. This study was to investigate the effect of these three synthetic compounds on the Ca[superscript 2+] entry into aortic smooth muscle cells after noradrenaline-induced depletion of intracellular Ca[superscript 2+]. Thoracic aortic strips were isolated from male Wistar rats (250-300g), denuded the endothelium layer, and suspended in a 15 ml-organ bath containing physiological solution. In order to deplete intracellular Ca[superscript 2+], noradrenaline (1 muM) was added to stimulate the aortic contraction in the Ca[superscript 2+]-free medium. After the intracellular Ca[superscript 2+] was completely depleted, the aortic strips were washed 3 times with Ca[superscript 2+]-free medium. Upon addition of Ca[superscript 2+], the spontaneous contraction or resting tone (RT) of rat aortic strip was observed. This process was inhibited by prazosin (1 muM) and nifedipine (1 muM). Our results showed that CU 18-08 (10 muM) and CU 18-10 (10 muM) significantly inhibited the RT while CU 18-11 did not. These findings suggested that CU 18-08 and CU 18-10 interfered the mechanical Ca[superscript 2+] refilling process into intracellular stores. It is possible that these two compounds may have pharmacological blocking effect on voltage-operated Ca[superscript 2+]channels or Ca[superscript 2+] entry due to a-adrenoceptor activation. CU 18-08 and CU 18-10 significantly inhibited contraction induced by KCl 40 mM and suppressed the cumulative dose response curve induced by CaCl2 in Ca[superscript 2+]-free depolarizing solution. CU 18-10 significantly inhibited contraction induced by TEA 1 mM. These findings suggest that CU 18-08 and CU 18-10 may interfere the entry of Ca2+ into intracellular space. In contrast, CU 18-11 potentiated the effect of noradrenaline in activation of contraction response. It is possible that CU 18-11 may increase Ca[superscript 2+] influx through voltage-operated Ca[superscript 2+] channels or alpha-adrenoceptors.