Masaru Kantoh

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.

Differences between muscular receptors and neurnal receptors for cholecystokinin-octapeptide in the guinea-pig gallbladder

To investigate the differences between muscular and neural receptors for cholecystokinin-octapeptide (CCK-OP) in the guinea-pig gallbladder, we studied the effects of dibutyryl cyclic GMP (dbc GMP) on CCK-OP-evoked contraction and [3H]acetylcholine (ACh) release. 10(-3) M dbc GMP significantly reduced CCK-OP (10(-8) M)-evoked contractions without affecting the peptide-induced [3H]ACh release. It is suggested that there are two types of CCK-OP receptors in the guinea-pig gallbladder (dbc GMP-sensitive muscular receptors and dbc GMP-insensitive neural receptors).

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.

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.

Ultrasound measurement of contractile motility of the gallbladder after vaious gastric surgery.

過去1カ月以内に, 胃切除術を施行された患者44名 (良性疾患13名, 悪性疾患31名) を対象に, 乾燥卵黄製剤 (ダイヤン) 経口投与後の胆のう収縮運動を超音波映像下に観察した.胆のうの最大収縮率は健常者 (10名) に比べ, 悪性疾患で有意に低下し, 特にBillroth II法による再建術を受けた群で, 収縮不全が顕著であった (p<0.01).naloxone (0.4mg) の筋肉投与は胃癌手術後の収縮不全を有意に改善した (p<0.01).以上の事実より, ダイヤン投与後の胆のう収縮機能に関して, リンパ節郭清による神経の切離と, 再建術式による食物の十二指腸通過の有無が重要であり, 内因性opioidの過剰やcholecystokinin (CCK) 放出の低下が関与する可能性が示唆された.

Ultrasound measurement of contractile motility of the gallbladder after subtotal gastrectomy.

胃切除後に高頻度に発生する胆のう疾患の原因を収縮運動の面から考察する目的で, 過去1ヵ月以内に, 胃癌で胃亜全摘術を施行された患者18名を対象に, ダイヤン経口負荷後の胆のう収縮運動を, 経時的に超音波診断装置にて観察した. 胃亜全摘後には, 胆のう収縮能の低下がみられたが, 特にBillroth II法による再建術を受けた群では, Billroth I法に比べ, 空腹時胆のう面積は拡張し, ダイヤンによる収縮能も極めて不良であった. 胃癌手術時には, 胃切除に加え, リンパ節郭清に伴い, 迷走神経や交感神経の切離も施行され, これら種々の要因が術後の胆のう機能低下に関与していると考えられるが, 特に再建術式による食物の十二指腸通過の有無が重要と考えられた.