Maselli M A, Piepoli A L, Pezzolla F, Caruso M L, Lorusso D
Laboratory of Experimental Pathophysiology and Pharmacology, Italy.
Neurogastroenterol Motil. 1999 Feb;11(1):47-53. doi: 10.1046/j.1365-2982.1999.00134.x.
In vivo studies have demonstrated that somatostatin induces human gallbladder relaxation. To determine whether this polypeptide acts directly on the gallbladder muscle, its effect on strips of human gallbladder was studied in vitro. Strips of gallbladder were set up isometrically in an organ bath containing oxygenated Krebs' solution. Dose-response curves to cholecystokinin-octapeptide and carbachol were first established. The ability of somatostatin to cause relaxation under basal conditions and during 50% maximal stimulation by cholecystokinin-octapeptide (7.2 x 10(-8) M) and carbachol (3.5 x 10(-6) M) was assessed in 32 strips at 4.3 x 10(-6) M concentration which mimics the plasma concentrations found in patients with somatostatinoma and in 12 additional strips at 4.3 x 10(-8) M concentration. Somatostatin action on the intrinsic innervation by using electrical field stimulation (EFS) (200 mA 5 msec in duration, 30 Hz; 400 mA, 1 msec in duration, 10 Hz) was also evaluated in 39 strips. Somatostatin had no effect on the basal or carbachol-generated tensions. On the contrary, somatostatin (4.3 x 10(-6) M) reduced cholecystokinin-octapeptide-generated tensions by 8% (P < 0.001) and reduced EFS-generated tensions at 30 Hz by 7.7% (P < 0.01) and those at 10 Hz by 41.2% (P < 0.01). All responses to cholecystokinin-octapeptide and carbachol were abolished by dibutyryl-guanosine 3', 5'-cyclic monophosphate (5 x 10(-3) M) and atropine (10(-5) M), respectively (P < 0.0002 and P < 0.0002). All responses to electrical field stimulation were reduced or abolished by tetrodotoxin (2 x 10(-6) M) (P < 0.001 and P < 0.0001, respectively). Our findings show that somatostatin exerts its inhibitory action on the response to cholecystokinin-octapeptide and on the intrinsic innervation of the gallbladder smooth muscle. The probable neurotransmitter is the acetylcholine.
体内研究表明，生长抑素可诱导人胆囊舒张。为确定该多肽是否直接作用于胆囊肌肉，我们在体外研究了其对人胆囊条带的影响。将胆囊条带等长地置于含有充氧克雷布斯溶液的器官浴中。首先建立了对八肽胆囊收缩素和卡巴胆碱的剂量反应曲线。在32条胆囊条带中，以4.3×10⁻⁶ M的浓度评估生长抑素在基础条件下以及在八肽胆囊收缩素（7.2×10⁻⁸ M）和卡巴胆碱（3.5×10⁻⁶ M）50%最大刺激时引起舒张的能力，该浓度模拟生长抑素瘤患者血浆中的浓度；在另外12条胆囊条带中，以4.3×10⁻⁸ M的浓度进行评估。还在39条胆囊条带上评估了生长抑素通过电场刺激（EFS）（200 mA，持续5毫秒，30 Hz；400 mA，持续1毫秒，10 Hz）对内在神经支配的作用。生长抑素对基础张力或卡巴胆碱引起的张力无影响。相反，生长抑素（4.3×10⁻⁶ M）使八肽胆囊收缩素引起的张力降低8%（P<0.001），使30 Hz时EFS引起的张力降低7.7%（P<0.01），使10 Hz时EFS引起的张力降低41.2%（P<0.01）。对八肽胆囊收缩素和卡巴胆碱的所有反应分别被二丁酰环磷腺苷（5×10⁻³ M）和阿托品（10⁻⁵ M）消除（P<0.0002和P<0.0002）。对电场刺激的所有反应均被河豚毒素（2×10⁻⁶ M）降低或消除（分别为P<0.001和P<0.0001）。我们的研究结果表明，生长抑素对八肽胆囊收缩素的反应以及对胆囊平滑肌的内在神经支配发挥抑制作用。可能的神经递质是乙酰胆碱。
