Theobald R J
Department of Pharmacology, Kirksville College of Osteopathic Medicine, MO 63501.
Eur J Pharmacol. 1992 Dec 15;229(2-3):125-30. doi: 10.1016/0014-2999(92)90545-f.
Purines have been shown to inhibit and excite feline detrusor smooth muscle through P1 and P2 receptor activation. Several recent studies have demonstrated differences in agonist potency orders for subclasses of purinoceptors, including P2Y and nucleotide, or P2U receptors. The current studies were performed to determine the presence of such receptor subtypes in feline detrusor smooth muscle. Cats were surgically prepared for monitoring detrusor smooth muscle contractions as increases in intravesical pressure. Contractions were induced by pelvic nerves stimulation (PNS), ATP, and ATP analogs, such as beta, gamma-methylene ATP (APPCP), 5' adenylimido diphosphate (AMP-PNP) and 2-methylthio ATP (2-MeSATP), ATP gamma S, UTP, CTP and GTP. These agents all produced contractions and had an agonist potency order of AMP-PNP = APPCP > ATP gamma S = 2-MeSATP >> ATP > UTP = CTP = GTP. The agonist potency order for inhibition of PNS nerve-evoked bladder contractions was APPCP = AMP-PNP = ATP gamma S > 2-MeSATP = ATP > UTP = CTP = GTP. Reactive Blue 2 and Coomassie's Brilliant Blue G, two putative P2Y receptor antagonists, antagonized purine-induced actions. This antagonism and the agonist potency orders suggest the possible presence of novel receptors in detrusor smooth muscle and/or the presence of multiple receptors in detrusor smooth muscle.
嘌呤已被证明可通过激活P1和P2受体来抑制和兴奋猫的逼尿肌平滑肌。最近的几项研究表明，嘌呤受体亚类（包括P2Y和核苷酸或P2U受体）的激动剂效力顺序存在差异。进行当前研究以确定猫逼尿肌平滑肌中此类受体亚型的存在。通过手术准备猫，以监测逼尿肌平滑肌收缩，即膀胱内压的升高。通过盆腔神经刺激（PNS）、ATP和ATP类似物（如β,γ-亚甲基ATP（APPCP）、5'-腺苷亚氨基二磷酸（AMP-PNP）和2-甲基硫代ATP（2-MeSATP）、ATPγS、UTP、CTP和GTP）诱导收缩。这些药物均产生收缩，其激动剂效力顺序为AMP-PNP = APPCP > ATPγS = 2-MeSATP >> ATP > UTP = CTP = GTP。抑制PNS神经诱发膀胱收缩的激动剂效力顺序为APPCP = AMP-PNP = ATPγS > 2-MeSATP = ATP > UTP = CTP = GTP。两种假定的P2Y受体拮抗剂活性蓝2和考马斯亮蓝G可拮抗嘌呤诱导的作用。这种拮抗作用和激动剂效力顺序表明逼尿肌平滑肌中可能存在新型受体和/或逼尿肌平滑肌中存在多种受体。
