본 실험에서는 흰쥐의 뇌 기저동맥을 이용하여 K<sup>+</sup>과 U46619에 의한 수축과 세포내 Ca<sup>2+</sup>의 변동을 관찰하고, 이들 반응을 CGRP 전처치시 나타나는 반응과 비교하였다. CGRP (30과 100 nM)는 U46619에 의하여 야기된 수축반응과 세포내 Ca<sup>2+</sup>의 증가반응을 억제시켰으나, K<sup>+</sup> (90 mM)에 의하여 나타나는 반응에는 영향을 미치지 아니하였다. 게다가, U46619에 의하여 야기되는 장력에 대하여 세포내 Ca<sup>2+</sup>의 변동 (F<sub>340</sub>/F<sub>380</sub>)을 도표화하여 세포내 Ca<sup>2+</sup> 농도와 장력의 발생과의 상관관계를 검토하고, 이들 결과를 CGRP 전처치시 나타나는 결과와 비교하였다. CGRP (30과 100 nM) 전처치군에서 얻어진 직선이 오른쪽으로 치우치지는 않으면서 아래쪽으로 이동하는 점으로 볼 때, CGRP가 Ca<sup>2+</sup>에 대한 수축기구의 감수성에는 영향을 미치지 않으면서 세포내 Ca<sup>2+</sup> 농도를 저하시킴에 의하여 U46619에 의한 근수축반응을 억제시키는 것으로 보여진다. 이러한 CGRP의 효과는 CGRP1 수용체 길항제인 CGRP(8 ~ 37) 분획(100 nM)의 전처치시 현저히 억제되었다. CGRP에 의한 수축력과 세포내 Ca<sup>2+</sup>의 저하는 large conductance Ca<sup>2+</sup>에 의하여 활성화되는 K<sup>+</sup> 통로 봉쇄제인 charybdotoxin (100 nM)과 iberiotoxin (100 nM)의 전처치에 의하여 완전하게 역전되었으나, small conductance Ca<sup>2+</sup>에 의하여 활성화되는 K<sup>+</sup> 통로 봉쇄제인 apamin (300 nM)과 ATP에 감수성이 높은 K<sup>+</sup> 통로 봉쇄제인 glibenclamide (1 μM)에 의해서는 영향을 받지 아니하였다. 이상의 결과로 볼 때 CGRP1 수용체는 Ca<sup>2+</sup>에 의하여 활성화되는 K<sup>+</sup> 통로를 개방시킴으로 세포내 Ca<sup>2+</sup>을 감소시켜 뇌 기저동맥의 이완반응을 매개하는 것으로 사료된다.
In the present study, we observed change in intracellular Ca<sup>2+</sup>([Ca<sup>2+</sup>]<sub>i</sub>) as measured with the fluorescent Ca<sup>2+</sup>-indicator fura-2 in association with force development of the rat basilar arteries during activation byK<sup>+</sup> depolarizing solution and U46619, a thromboxane analogue, in the absence and the presence of calcitonin-gent related peptide (CGRP). CGRP (30 and 100 nM) caused a concentration-dependent inhibition of U46619-induced contraction with decrease in [Ca<sup>2+</sup>]<sub>i</sub>, whereas it did not exert any effect on the K<sup>+</sup> (90 mM)-induced contraction and increase in [Ca<sup>2+</sup>]<sub>i</sub>, Further, [Ca<sup>2+</sup>]<sub>i</sub>-force relationships were determined by plotting the ratio of F<sub>340</sub>/F<sub>380</sub> ([Ca<sup>2+</sup>]<sub>i</sub>) as a function of the force induced by U46619, and the results were compared with those obtained in the presence of CGRP. The curves obtained in the presence of CGRP (30 and 100 nM) were significantly moved to downward without right shift of the curves suggesting that CGRP inhibited the U46619-induced contraction only by mediation of reduction in [Ca<sup>2+</sup>]<sub>i</sub> with out any change in the sensitivity of contractile apparatus to Ca<sup>2+</sup>. The CGRP-induced attenuation of [Ca<sup>2+</sup>]<sub>i</sub> and force development was significantly inhibited under pretreatment with CGRP (8 ~ 37) fragment (100 nM), a CGRP1 receptor antagonist. Both the reduced contraction and reduction in [Ca<sup>2+</sup>]<sub>i</sub> caused by CGRP were fully reversed by pretreatment with charybdotoxin (100 nM) and iberiotoxin (100 nM), large conductance Ca<sup>2+</sup>-activated K<sup>+</sup> channel blockers, but not by apamin (300 nM), a small conductance Ca<sup>2+</sup>-activated K<sup>+</sup> channel blocker, and glibenclamide ( 1 μM), an ATP-sensitive K<sup>+</sup> channel blocker. In conclusion, it is suggested that the CGRP1 receptor, upon activation by CGRP, are coupled to opening of Ca<sup>2+</sup>-activated K<sup>+</sup> channel and cause to decrease in [Ca<sup>2+</sup>]<sub>i</sub>, thereby leading to vasodilation of the rat basilar artery. However, it is not defined that the mechanism underlying vasodilation whether the K<sup>+</sup> channel blockers, charybdotoxin and iberiotoxin directly block the CGRP receptors and that CGRP-evoked relaxation is dependent on the cyclic AMP or K<sup>+</sup> channel opening or both actions.