Toku Takahashi

Cholecystokinin octapeptide-evoked [3H]acetylcholine release from guinea pig gallbladder

Cholecystokinin-octapeptide (CCK-OP) produced a contractile response in isolated guinea pig gallbladder; the response consisted of scopolamine-sensitive and scopolamine-insensitive components, neither of which were affected by tetrodotoxin or hexamethonium. In the presence of tetrodotoxin, CCK-OP evoked [3H]acetylcholine (ACh) release from strips of gallbladder in a concentration-dependent manner. These results suggest that CCK-OP acts at two sites in the guinea pig gallbladder, viz. the smooth muscle cell and the postganglionic cholinergic nerve terminal.

Bombesin evoked acetylcholine release from the guinea pig antrum.

Bombesin induced contraction and acetylcholine (ACh) release of the longitudinal muscle strip of the guinea pig antrum were examined using the standard organ bath technique and the superfusion system. Bombesin increased frequency and tonus of rhythmic contraction in a dose dependent manner (10(-10)M - 10(-7)M). The effects of bombesin on frequency of contraction were not affected by atropine, propranolol, phentolamine, hexamethonium and tetrodotoxin. The effects on tonus, on the other hand, were significantly reduced by atropine, and the dose response curve to bombesin was shifted to the right. There was a remarkable increase of 3H-ACh release by the superfusion of bombesin (10(-8)M), which was almost completely abolished in Ca-free medium, but not affected by hexamethonium and tetrodotoxin. These results suggest that mechanism of bombesin effects on frequency is different from that on tonus; frequency response to bombesin is not dependent on autonomic nervous system but due to a direct effect on smooth muscle cells, whereas tonic response to the peptide is partly mediated by ACh release via a mechanism independent of sodium spike.

Human pancreatic polypeptide, neuropeptide Y and peptide YY reduce the contractile motility by depressing the release of acetylcholine from the myenteric plexus of the guinea pig ileum

SummaryTransmural stimulation (TS; 15 V, 0.5 msec, 1–5 Hz, for 30 sec) caused a contraction in a frequency-dependent manner of the longitudinal muscle with myenteric plexus of the guinea pig ileum. Two-min premedication with human pancreatic polypeptide (HPP, 10-8 M-10-6), neuropeptide Y (NPY, 10-8 M-10-6 M), and peptide YY (PYY, 10-8 M-10-6M) partially, by less than 35%, reduced TS (15 V, 0.5 msec, 10 Hz)-evoked contraction in a dose-dependent manner without affecting the resting tensions. Hexamethonium, phentolamine, prazocine, yohimbine, propranolol, naloxone and theophylline had no effects on the inhibitory actions of these peptides on TS-evoked contractions. TS (15 V, 0.5 msec, 10 Hz)-evoked3H-ACh release was significantly reduced by 2-min premedication of HPP (10-6 M), NPY (10-6 M) and PYY (10-6 M). The order of potency of these depressant effects on TS-evoked contraction and3H-ACh release was PYY> NPY> HPP. It is suggested that the members of PP family have inhibitory effects on the contractile motility by depressing ACh release from myenteric plexus of the guinea pig ileum.

Hepatobiliary and gastrointestinal imaging after pancreaticoduodenectomy —A comparative study on Billroth I and Billroth II reconstructions

This study was conducted to compare the passage of bile and food through the remnant alimentary tract between 2 and 6 months following pancreaticoduodenectomy in patients undergoing Billroth I (Imanaga) and Billroth II (Child) reconstructions, using dual scintigraphy. In the patients who underwent Childs operation (n=14), hepatobiliary scintigraphy showed a prominent stasis of bile tracer in the proximal jejunal loop and a significant time delay before the bile and food became mixed at the upper jejunum. On the other hand, in the patients who underwent Imanagas operation (n=9) no bile stasis in the proximal jejunal loop was found and the time taken before the two agents became mixed was similar to that of healthy controls (n=7). The time taken for the two agents to mix at the upper jejunum was 65.8±7.9 min in the patients after Childs operation, 17.3±2.5 min in those after Imanagas operation, and 18.5±2.8 min in the healthy controls, respectively. Continuous stasis of bile in the proximal loop and severe postcibal asynchronism in patients who undergo Childs operation can therefore cause reflux cholangitis and absorptive disturbances in the long postoperative term. The results of this study suggest that Imanagas reconstruction is a more physiological procedure than Childs reconstruction following pancreaticoduodenectomy.

Effects of cholecystokinin-octapeptide on the human gallbladder both in vivo and in vitro

SummaryTo determine the sites and mechanisms of action of cholecystokinin-octapeptide (CCK-OP) on the human gallbladder, effects of atropine sulfate on CCK-OP-evoked contractions were studied in both in vivo and in vitro experiments. In vivo studies performed by means of real time ultrasonography in six healthy volunteers showed remarkable contractions of the gallbladder after intramuscular injection of CCK-OP (0.07 Μg/kg), which was nearly abolished by premedication of atropine sulfate (0.015 mg/kg). Atropine sulfate (10-6 M) slightly but significantly reduced CCK-OP (10-11M-3 x 10-7 M) induced contractions and the dose-response curve for CCK-OP was shifted to the right of the muscle strips of the human gallbladders. It is suggested that CCK-OP acts mainly on cholinergic neurons in vivo. On the contrary, the most sensitive sites of action of CCK-OP might be smooth muscles rather than cholinergic neurons in vitro.

Follow up studies on various reconstruction methods of the biliary tract including our new method (Roux Y-duodenojejunal anastomosis)

Thirty six patients with benign diseases of the biliary tract (14 patients with congenital choledochal dilatation, 15 patients with postoperative stricture and 7 patients with others) were divided into three groups: 21 patients who underwent a Roux Y (RY), 7 patients who underwent a jejunal interposition (IP) and 8 patients who underwent a side to side anastomosis between the jejunal limb of the Roux Y and the duodenum (RY-DJ). The RY-DJ was designed to decompress the Roux Y jejunal limb and to allow an inflow of bile into the duodenum. Significant complications, including cholangitis, infection, or abdominal pain, developed in 10 of the patients with RY (48 per cent), 7 of the patients with IP (100 per cent) and 1 of the patients with RY-DJ (13 per cent). None had a postoperative peptic ulcer. Simultaneous scintigraphy showed the time required for the two agents,99mTc-IDA and111In-DTPA, to mix at the upper jejunum, which revealed that the time taken by the patients with RY-DJ was similar to that of the patients with IP and to that of healthy controls. The time was markedly longer in the patients with RY, presumably due to a prominent stasis of the bile tracer in the Roux Y jejunal limb. Our new method (RY-DJ) for reconstruction of the extrahepatic biliary tract is more physiological and has less postoperative complications than other conventional methods.

Progesterone inhibits the contractile motility of the guinea pig gallbladder

We studied the effects of progesterone on the contractile motility of the guinea pig gallbladderin vitro. Carbachol (10−6 M) induced contractions were reduced by the pretreatment with progesterone (10−8–10−6 M) in a dose-dependent manner. Concentration-response curves for carbachol, histamine and CCK-OP showed inhibition by progesterone (5×10−7 M). These results suggest that progesterone has a direct inhibitory effect on gallbladder smooth muscle. Contractile responses to potassium (10–60 mM) or calcium (0.4–3.2 mM), which were thought to activate the contractile machinery by increasing the influx of extracellular calcium, were not affected by the pretreatment of progesterone. The direct inhibitory effects of progesterone on gallbladder smooth muscle might be explained by the inhibition of calcium release from the intracellular storage sites.

Different innervation mechanisms between the lesser and greater curvature of guinea pig antrum.

Transmural stimulation (TS) produced a frequency-dependent contraction of the longitudinal muscles from the lesser curvature of the guinea pig antrum, which was abolished by atropine. On the other hand, a response to TS of the strips from the greater curvature was biphasic: a rapid contraction followed by a relaxation, which was abolished by tetrodotoxin. By pretreatment with atropine, rapid contraction of the biphasic response evoked by TS in the greater curvature was abolished and relaxation was augmented. Relaxation to TS of the greater curvature was not affected by prazocine, yohimbine, phentolamine, propranolol, theophylline, apamin, α-chymotrypsin, and vasoactive intestinal polypeptide receptor antagonist. Different innervation mechanisms were suggested to be present in the longitudinal muscles between the lesser curvature (innervated with excitatory cholinergic neurons) and the greater cuvature (innervated with excitatory cholinergic neurons and nonadrenergic inhibitory neurons) of the guinea pig antrum.