흰쥐 말초혈액 T-림프구에서 Vasoactive Intestinal Polypeptide의 효과에 대한 Propranolol의 억제 기전

• 영문명: Inhibitory Mechanism of Propranolol on the Effects of VIP in Peripheral Blood T-lymphocytes of Rat
• 발행기관: 대한약리학회
• 저자명: 안영수(Young Soo Ahn) 추성이(Sung Yee Choo) 강동원(Dong Won Kang) 이상헌(Sang Hun Lee)
• 간행물 정보: 『대한약리학잡지』제31권 제2호, 219~232쪽, 전체 14쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 1995.09.30

영문 초록

Vasoactive intestinal polypeptide(VIP) and β-adrenergic agonists have immunomodultory effects on the peripheral blood T-lymphocytes of rat through their own receptors. Both of them utilize the same signal transduction pathway. That is, the stimulatory guanine nucleotide binding protein(G protein) mediates the receptor-adenylyl cyclase coupling, producing intracellular increase of cyclic adenosine monophosphate(cAMP). In the previous experiment, propranolol, a β-adrenergic receptor blocker, inhibited the VIP-induced protein phosphorylation in lymphocytes. However, propranolol could not block the effect induced by forskolin. Therefore, this study was designed to elucidate the mechanism of the inhibitory action of propranolol on the effects of VIP. Using peripheral blood lymphocytes of rats, the effect of propranolol on the receptor binding characteristics of VIP was observed. And the effects of propranolol were compared to the effects of timolol on the cAMP increase induced by isoproterenol, VIP or forskolin. The results obtained are as follows. 1) Receptor binding study showed no significant differences in the affinity or density of VIP receptor between the control and propranolol-pretreated groups. 2) VIP-induced increase of cAMP was inhibited by propranolol, but not by timolol. 3) Both propranolol and timolol suppressed the isoproterenol-induced cAMP increase. 4) Propranolol also inhibited the histamine-induced cAMP increase. 5) Propranolol did not inhibit the increase of cAMP stimulated by forskolin. 6) Lidocaine did not block the VIP-induced cAMP increase. These results show that the inhibitory mechanism of propranolol is not related to β-adrenergic receptor or its membrane stabilizing effect, and it is suggested that propranolol can block the effects of VIP by inhibiting the intermediate step between the VIP receptor and adenylyl cyclase.

키워드

VIP receptor Propranolol Cyclic AMP Lymphocytes