Recently, function-preserving operations have become popular, and pylorus-preserving pancreatoduodenectomy (PPPD) is frequently performed for diseases of the head of the pancreas. However, there are only a few basic studies on the pyloric function after PPPD. Using strain gauge force transducers (SGTs), we studied the pyloric motility of normal and PPPD dogs. We prepared three normal and three PPPD dogs in which the SGTs were implanted onto the antrum and pyloric ring, etc. In conscious dogs, the spontaneous gastrointestinal motility was recorded, and the plasma motilin concentration was measured during the interdigestive state. Following the administration of exogenous Leu¹³-motilin, the motility was again recorded. The relaxation and opening of the pyloric ring was observed synchronously with intense contractions of the antrum during the phase III of normal dogs. Phase III-like motility was recorded in the PPPD dogs, which was not a typical periodic motility. The plasma motilin concentration of one PPPD dog could be measured, and the motilin levels during the phase III-like motility were higher than during phase I. The phase III-like motility was induced by Leu¹³-motilin in both normal and PPPD dogs. The phase III-like motility recorded in the PPPD dogs was not a typical periodic one, and this aberrant motility was considered to be one of the causes of delayed gastric emptying. Phase III-like motility was induced by the administration of Leu¹³-motilin; therefore, it is possible that Leu13-motilin improved the motility of the pyloric ring after PPPD.

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1. In smooth muscles isolated from the guinea-pig trachea, the effects of dihydropyridines, nifedipine and nicardipine on contractions produced by carbachol (Cch) were studied in normal (6mM) and excess K⁺ concentration (60mM). The tonic contraction produced by 1μM Cch was highly dependent on the external Ca²⁺ concentration ([Ca²⁺] ₀) and was not significantly affected by cyclopiazonic acid or thapsigargin, Ca²⁺ uptake inhibitor.
2. [Ca²⁺] ₀-tension curves were steeper in the presence of 1μM Cch (the Hill coefficient: 2.5) than in the presence of 60mM K⁺ (Hill coefficient: 1.6) and their ED₅₀ of Ca²⁺ was 0.16 and 0.39mM, respectively. An increase of K⁺ to 60mM in the presence of 1μM Cch shifted the curve to the left roughly in parallel (ED₅₀: 0.12mM, Hill coeffcient: 2.3).
3. [Ca²⁺] ₀-tension curve in the presence of 1μM Cch was shifted to the right in parallelby nifedipine (1μM). This was markedly potentiated by 60mM K⁺ (the increase in ED₅₀ of Ca²⁺being 3 times at 6mM and 15 times at 60mM K⁺). No tension was evoked by Ca²⁺ up to 2.5mM in 60mM K⁺ solution containing 1μM nifedipine but no Cch.
4. In the absence of nifedipine, Cch-induced contractions were potentiated by 60mM K⁺, whereas in the presence of nifedipine, Cch-induced contractions were markedly inhibited by 60mM K⁺. These mechanical changes were accompanied by an increase or a decrease in intracellular Ca²⁺.
5. A hypothesis is presented to explain the results which suggests that the kinetics of Ca²⁺ influx though a single type of pathway is modulated by membrane potential and receptor activation and that the susceptibility of the pathway to dihydropyridine blockade is closely related to the Ca2+ influx kinetics with receptor activation reducing and membrane depolarization increasing the susceptibility.

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In smooth muscle cells isolated from cerebral blood vessels, histamine activates Cl^- channels through an elevation of intracellular Ca²⁺. We investigated whether Cl^- currents were also evoked by adenosine triphosphate (ATP) or caffeine in isolated smooth muscle cells from the rabbit basilar artery using the perforated patch-clamp technique. Bath application of 10μM ATP or 1 mM caffeine (holding potential -60 mV) activated transient inward currents. With prolonged bath application of 10 μM ATP or 1 mM caffeine, oscillatory inward current were sporadically generated. At a holding potential of -40 mV, transient Cl^- currents were induced by 10μM histamine, 10μM ATP, and 1 mM caffeine, following activation of a K⁺ current. At -10 or -20 mV, histamine predominantly activated the K⁺ current. A repetitively activated outward current was induced by membrane depolarization. These results suggest that oscillations in intracellular Ca²⁺ induced by histamine, ATP, and caffeine caused Cl^--current activation at the resting membrane potential. This Cl^- current may depolarize the membrane and, thus activate voltage-dependent currents, including a Ca²⁺-dependent K⁺ current. Both the Ca²⁺-dependent K⁺ and Cl^- currents induced by various stimuli may contribute to the modulation of Ca²⁺ influx by reinforcing membrane depolarization.

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Potentiating actions of external lanthanum (La³⁺) on muscarinic receptor-activated nonselective cation current (I^cat) were investigated in myocytes dissociated from the longitudinal muscle layer of guinea-pig ileum, with a whole-cell variant of the patch clamp technique. I_cat was dissected from other membrane currents by loading Cs-aspartate into the cell. Application of submilimolar collcentratiohs of La³⁺following 300μM ACh intothe bath caused a dose-dependent increase in the amplitude of I_cat. The apparent Kd valuefor this increase was 190μM, with a cooperativity factor of 1.7. La³⁺-induced increase in I_cat amplitude was not associated with either changes in the reversal potential of I_cat or altered sensitivity of muscarinic receptor to ACh, and paralleled by the conductance increase of I_cat, the maximum of which (G_max) occurred at about 1 mM La³⁺. Voltage-jump experiments revealed that the rate of current relaxation at hyperpolarizing potentials was greatly reduced in the presence of La³⁺, and correspondingly the steady state activation curve shifted toward more negative potentials. Divalent cations such as Cd²⁺ or Ni²⁺, which have been known to block I_cat, antagonized the augmentative effect of La³⁺ on I_cat in a competitive fashion, suggesting that the site of their actions might be similar. Furthermore, single I_cat activities induced by internal perfusion of GTPγS (100μM) was also greatly enhanced by external addition of 1 mM La³⁺. Under current clamp conditions, 1 mM La³⁺ blocked spontaneous Ca²⁺ spike activities, but was almost without effect on the membrane depolarization induced by ACh. In contrast, milimolar concentrations of Cd²⁺ and Ni²⁺ abolished both Ca²⁺ spike activities and ACh-induced depolarization. Potential importance of La³⁺ as a tool to investigate the external Ca²⁺-dependence of I_cat has been discussed.

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The gastric emptying of indigestible solids is affected by the size, specific gravity, shape, consistency and the compressibility of the indigestible solids and depends largely on the composition of the meal. The threshold size is about 3.0mm in canine. But it is reported that the estimates made for dogs may not apply to humans. I evaluated whether the size of indigestible solids affects gastric emptying in healthy subjects with food which had the same specific gravity as the indigestible solids. We used three sets of 20 ring shaped radiopaque markers, which had the same specific gravity (1.2), shape, consistency, and compressibility, but different diameters (2.0mm, 4.5mm and 7.0mm). After the subjects ingested the three sets of 20 markers with food, the number of markers evacuated from the stomach was counted every 15min until all the markers were evacuated. The median numbers of discharged markers of 2.0mm, 4.5mm and 7.0mm were 5 (0-5), 1 (0-3) and 3 (0-4) at 60min, 15 (3-18), 10 (6-9) and 13 (11-16) at 120min (median, 25th-75th percentile), respectively. There was no statistically significant difference between the numbers of the three types of discharged markers during observation. The lag time (the period from the time of ingestion of the markers to the time when the first marker left the stomach) of the 2.0mm, 4.5mm and 7.0mm markers was 52.5 (45-105), 67.5 (60-105), and 52.5 (45-105) min, respectively, and there was no statistically significant difference. In conclusion, the radiopaque markers of different diameters (below 7.0mm) left the stomach in the same pattern.

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