Discharge patterns and CO₂-responsiveness of the efferent respiratory activities in the superior laryngeal (Xsl), hypoglossal (XII), and phrenic (Phr) nerves were compared between vagi-intact and -denervated rats. Bilateral cervical vagotomy decreased the respiratory frequency (f), minute Phr activity (peak integrated Phr activity × f) and consequently elevated end-tidal P_co2 (PET_co2). Augmentation of the peak inspiratory activity following vagotomy was much larger in the Xsl and XII nerves than that in the Phr nerve. After vagotomy, the time delay from the onset of inspiratory activities in the Xsl or XII nerve to the onset of the Phr bursts was greatly prolonged. While in the vagi-intact rats the peak inspiratory activities of these cranial nerves were not increased in response to elevated PET_co2, the activities, in particular of the XII nerve, were augmented by high PET_co2 in the absence of vagal afferents. These results suggested that the vagal afferents inhibit not only phasic Phr discharges but also inspiratory output neurons in the Xsl or XII motor nuclei being activated in normo- and hypercapnia and that they facilitate temporally the onset and progress of inspiratory activities in various groups of respiratory output neurons.

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The activation of cyclic AMP-dependent protein kinase by catecholamines was measured to study the involvement of this enzyme in a-amylase release in the rat parotid gland. Norepinephrine (NE) rapidly increased the activity of protein kinase, and the stimulated activity of protein kinase as well as cyclic AMP accumulation rapidly returned to a basal level after addition of alprenolol. Isoproterenol was about 10 times more potent than NE in both activating protein kinase and stimulating α-amylase release. Isobutyl-methylxanthine, which slightly increased the protein kinase activity, markedly increased the effect of NE. The maximum level of protein kinase activity obtained by the combined stimulation by NE plus isobutyl-methylxanthine was significantly higher than that by NE alone.β-Adrenergic antagonists inhibited more strongly the NE-induced activation of protein kinase than NE-induced α-amylase release. Inhibition of α-amylase release byβ-adrenergic antagonists was almost completely overcome by in creasing the concentration of NE, whereas that of protein kinase activity was not. Ten mm tolbutamide inhibited the effect of NE on α-amylase release without significantly changing the cyclic AMP accumulation and the activation of protein kinase by NE, although 20 mm tolbutamide was inhibitory to the effect of NE on all these parameters. Ten mm tolbutamide inhibited a-amylase release caused by carbamylcholine and methacholine. These results thus revealed discrepancies between the stimulation of α-amylase release and the activation of protein kinase by NE in some experimental conditions. It is suggested that, even though a cyclic AMP-protein kinase system is responsible for the regulation of α-amylase release by catecholamines, the process of α-amylase release may also be modulated by cyclic AMP-independent mechanisms.

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Sweat responses to mental arithmetic were recorded simultaneously on the axilla, palm, and general body surface (chest and forearm) by resistance or capacitance hygrometry at different ambient temperatures. Sweat expulsions observed on the axilla were fully synchronized with those on the general body surface, but not always with those on the palm. In some subjects the sweat responses to mental arithmetic on the general body surface were different in pattern from those on the palm. In such subjects the sweat response pattern on the axilla was similar to that on the general body surface. The sweat response to mental arithmetic occurred at a considerably lower environmental temperature on the axilla than on the general body surface. The occurrence of the sweat response on the axilla can be related to the peculiar feature of axillary thermal sweating: a lower threshold temperature and less responsiveness to thermal load compared with thermal sweating on the general body surface. This suggests that mental sweating on the axilla occurs due to the characteristic feature of thermal sweating on the axilla. Axillary eccrine sweating is not different qualitatively from sweating on the general body surface.

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The facilitatory action of tetraethylammonium (TEA) on endplate potentials (EPPs) and its depression by streptomycin (SM) were analyzed by recording EPPs from curarized frog muscles using conventional microelectrode techniques. The fractional release of transmitter was estimated from the early tetanic rundown of EPP during short train stimuli. To explain the marked facilitatory effect of TEA, on the fractional release and the antagonistic interaction of SM thereupon, it was postulated that to increase the evoked transmitter release, two molecules of TEA react with two sites in a still unidentified Casensitive component X of the transmitter-releasing mechanism. SM depresses the evoked transmitter release by competing with TEA for the occupancy of one of the two TEA sites. The equations derived from the present assumptions agreed reasonably well with the experimental results.

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We studied ATP and concentrations of other metabolites in cardiac and skeletal muscles from different species (frog, hamster, guinea-pig, and dog), using analytical capillary isotachophoresis. The method had several advantages for quantitative analysis of tissue metabolites tabolites: short separation time, high sensitivity, high resolution, and good reproducibility. It was also possible to detect a number of compounds pounds simultaneously, including ATP, ADP, AMP, cyclic AMP, creatine phosphate (CP), inosine monophosphate, NAD, NADH, glucose-6-phosphate, pyruvate, and inorganic phosphate. Generally, the concentrations centrations of high-energy phosphates (ATP and CP) in the cardiac muscle were significantly lower than those in the skeletal muscle, in all species tested, except for hamster where the concentration of CP in the skeletal muscle was comparable to that in the cardiac muscle. In mammals, ATP and CP concentrations were comparable in the atrium and ventricle while the concentration in the frog ventricle was significantly higher than that in the atrium. The data obtained by this isotachophoretic analysis were comparable to the data reported by the use of other conventional ventional analytical methods. The significance and reliability of isotachophoresis tachophoresis in the determination of the various metabolites in the cardiac diac muscle were discussed.

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Three reflex responses in the orbicularis oculi muscles were observed by electrical stimulation of the trigeminal nerve in lightly anesthetized or conscious cats. The third response, following the first and second responses, was concluded as being a “reactivated response” of the blink reflex as it was set up by the trigeminal afferent input evoked by the palpebral movement of the preceding blink. The reasons for this were as follows: 1) the third response disappeared on administration of muscle relaxants and 2) was enhanced by touching the palpebral hair ; 3) the palpebral movement activated the afferent discharges of the trigeminal exteroceptors which were strong enough to yield the reflex responses and 4) the latency of the first reflex response by the palpebral movement corresponded to the time lag between the preceding large reflex response and the third response; 5) the third response was hardly suppressed at all until the first response disappeared over a period of maximum reflex suppression following the conditioned stimulation of the trigeminal nerve.

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Acute effects of nicotine (NC) on the microcirculation of frog webs were studied by measuring the blood flow velocity in arterioles, and by determining the diameter of both arterioles and venules. Simultaneous recordings of the ventricular pressure and heart rate were obtained in order to compute the vascular resistance and to interpret the changes in microcirculation. The web of right hindlimb was immersed in a solution of NC (2.6 to 3.4 mg/ml) for 4 min. Blood flow velocity in web arterioles of left hindlimb was measured by means of a laser Doppler microscope. Internal diameters of web microvessels were determined using a micrometer on the ocular lens of the microscope. Mean flow velocity (MV) and pulsatile amplitude (PA) were calculated from the pulsatile flow-velocity contour for each vessel. Both MV and PA were increased after the immersion of the web in NC solution. Although the magnitude of the increment in MV was proportional to that in ventricular pressure, the vasodilation of both arterioles and venules and the flow rate in arterioles higher than the initial state continued even after the ventricular pressure had returned to the initial control value. Calculation of the relative change in vascular resistance in web arterioles following NC administration suggested a vasodilator response to NC. Furthermore, our results indicate that sufficient NC can be absorbed across the web epithelium to produce a systemic vascular response when the concentration of NC in the bathing solution is 2.6 mg/ml.

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1. Two identified Onchidium neurons are depolarized by glycine.
2. At low glycine concentrations, a phase of decrease in K⁺ permeability was dominant, while at relatively high concentrations of glycine, an increase in Na⁺ permeability became apparent. Strychnine suppressed the glycine-induced conductance increase but enhanced the phase of K⁺ permeability decrease; thus, the glycine depolarization was slightly increased.
3. A Hill plot was determined from the relationship between the relative increase in membrane conductance (Y) and the glycine concentration. The values of the Hill coefficient, n, and the apparent dissociation constant, K_A, were approximately 2 and 40 mM, respectively.
4. Amino acids other than glycine also produced a similar type of responses in these neurons. However, the increase in membrane conductance declined with the increase in the length of the side chain in each amino acid.
5. ACh initially produced hyperpolarization with an increase in membrane conductance, and then depolarization with a decrease in mem brane conductance. Glycine and ACh interacted in the phase of conductance increase, suggesting a common binding site.
6. The glycine responses were measured at pH 5.0-9.0. The glycineinduced conductance increase was augmented at higher pH, but depressed at lower pH.
7. Diisopropyl fluorophosphate (DFP; modifies serine or threonine residues) and pyridoxa1-5'-phosphate (PLP; modifies ε-amino groups of lysine residues) both reduced the glycine response. The Y-log [glycine] curves showed a parallel shift with both DFP and PLP toward higher glycine concentrations. The K_A increased leaving n unchanged. These competitive modes of inhibition suggested that the OH group in a serine or threonine residue and the ε-amino group of a lysine residue are the sites related to the binding of glycine at the receptor.
8. The modification of the carboxyl group by para-nitrothiophenol (p-NTP) decreased the glycine response. The K_A increased with decreased n. The non-competitive mode of inhibition suggested that the carboxyl groups probably constitute one of the negative charges included in the ionic channels for Na⁺
9. A schematic molecular model of the glycine receptor, in which the glycine binding sites and Na-channel are included, was made to explain all of the above-mentioned results.

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Changes in blood flow in different arteries occurring in the transposition response of the rat, induced by transposing the animal from a “home” cage to a new one, were studied using chronically implanted electromagnetic flow probes. In the response, hindquarter flow was increased by more than 50 %, superior mesenteric and renal flows were decreased by about 30 and 15 %, respectively, and common carotid flow remained almost unchanged. The increase in hindquarter flow in the response was much less after β-adrenoceptor blockade with propranolol. In adrenalectomized rats the flow changes in the hindquarter, mesenteric, and renal areas were less marked in either direction. These findings indicate that the blood flow redistribution in the transposition response is characterized by a shift of flow from the viscera to the skeletal muscles, in which the α- and β-effects of catecholamines released from the adrenal medulla in the response play a dominant role.

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The nonuniformity of dynamic mechanical responses along the length of stimulated frog sartorius muscle was examined by recording the length changes of muscle segments by means of streak photography. During isometric force development, the central or the pelvic end segment tended to shorten due to the stretching of the other segments. In muscles showing a marked nonuniformity in the segmental length changes occurring during isometric force development, there was also a marked nonuniformity in the segmental length changes occurring during stretches or releases applied at the plateau phase of an isometric tetanus. Marked nonuniform segmental length changes were also observed during afterloaded twitches and tetani. These results indicate that great care should be taken of the muscle segmental nonuniformity in heat and X-ray diffraction studies in which measurements are made using data obtained from a limited region of muscle. During the course of slow stretches or releases applied to tetanized muscles, the tibial and segment exhibited much smaller relative lengthening or shortening than the other segments when it had been appreciably stretched by the other segments during isometric force development. This might be associated with the formation of “locked-on” cross-links in the stretched segment.

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The effect of hypothermia on circulating blood volume wasstudied using 9 dogs subjected to body surface and blood cooling. Toanalyze the movement of water between the vascular and interstitial fluidspaces, Ringer solution was infused during normothermia and hypothermia (30°C core temperature). During body cooling and infusionexperiments, blood volume, hematocrit, and colloid osmotic pressurewere monitored continuously. When body temperature was loweredto about 30°C within 2 hr, plasma volume decreased from 39.0±0.1 to36.2±5.3 ml/kg and colloid osmotic pressure increased from 16.4±0.2 to17.0±3.1 mmHg. The changes in blood volume, colloid osmotic pressure, and central venous pressure during the infusion of Ringer solution andrecovery periods, were used for a simulation analysis based on a two-compartmentmodel. The instantaneous and delayed compliances were determinedon the vascular space and on the interstitial fluid space togetherwith the transvascular filtration coefficient of water. Hypothermia to30°C increased vascular compliance, but decreased interstitial fluidspace. The transvascular filtration coefficient of water decreased in hypothermia.These results suggest that the redistribution of blood dueto hypothermia causes a reduction of capillary area available for fluidexchange. The transvascular filtration coefficient determined on thewhole body decreases due to reduction of the compliances of the “effective” interstitial fluid space.

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The effects of Rb and Cs on the electrogenic Na-pump of the rabbit sinoatrial node cell were studied, using conventional microelectrode techniques. Hyperpolarizations induced by K or its substitutes were recorded from the preparations which were perfused previously with an extracellular K-free solution. The K-induced hyperpolarizations after K-depletion depended linearly on K-concentration in the range of 1.35 to 10.8 mm. When 2 mm Rb was used as an activator, a subthreshold oscillation appeared and the amplitude of the spontaneous action potentials in the Rb solution was larger than with the standard solution. As the concentration of Rb increased, the Rb-activated hyperpolarization increased, but the amplitude of the action potential decreased. In the case of Cs, the induced hyperpolarization was smaller than with K or Rb, and a transient recovery of pacemaker activity and gradual hyperpolarization preceded the true recovery in the standard solution. Since these yperpolarization effects were not observed after the application of ouabain-containing K-free solution, the hyperpolarizations were considered to be electrogenic. A small hyperpolarization induced by activation of the external site of the Na-pump appears to be necessary for the immediate recovery of automatism from arrest at low resting potentials.

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To examine physiological and pharmacological characteristics of synaptic transmission from taste cells to afferent nerve terminals in frog taste organ, changes in the glossopharyngeal nerve discharges and responses to chemical stimulation of the tongue were examined by intraarterially perfusing the tongue with Ringer solution containing monoamines and their related substances. Noradrenaline (NA), dopamine (DA), and adrenaline (AD) produced an increase in the spontaneous glossopharyngeal nerve discharges as well as an enhancement of taste responses to various kinds of chemical stimuli, but they did not affect tactile response. NA was the most effective of the three. Monoaminereleasing agents, tyramine and 6OHDA, enhanced spontaneous nerve discharges but depressed taste responses. Antimonoaminergic agents, phentolamine and phenoxybenzamine (α-blockers), increased nerve discharges and depressed taste responses, but did not affect tactile response. DCI (β-blocker), except at high concentrations, affected neither nerve discharges nor taste responses. Pre-treatment of frogs with monoamine-depleting agents, α-MPT and 6OHDA, depressed taste responses. Reserpine enhanced the effect of α-MPT. The depressed taste responses recovered after perfusion of the tongue with NA. From the results obtained, the possibility of NA being a transmitter at the afferent synapse in the frog taste organ was discussed.

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Intracellular membrane potential recording was attempted with pancreatic endocrine cells in monolayer culture. Morphologically identified A cells produced spike action potentials in response to injected electric current. The action potential was also evoked in the sodiumfree medium. It was concluded that pancreatic A cells are electrically excitable and probably generate Ca spike.

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The thrombolytic (fibrinolytic) effect of the urinary plasminogen activator, urokinase (UK), was compared with its fibrinogenolytic effect, using an artificial circulating system, and in in vivo pulmonary embolus and femoral vein thrombosis models. The thrombus lysing efficiency (fibrinolysis/fibrinogenolysis) was, in all cases, below 1.00, indicating that fibrinogenolysis is a primary function of UK while fibrinolysis is a secondary one.

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Cardiac output, ventilation volume and arterial pressure of an orthostatically unstable subject were recorded during an attack of vasovagal syncope induced by a passive tilt. The failure of circulatory homeostasis in the upright position may be ascribed to the depressor reflex initiated from the intracardiac baroreceptor.

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The geometric quantities of cross-sectional area, volume, and surface area have been calculated, to three-decimal-place accuracy, using the normal range of dimensional values for mammalian red blood cells. The calculations are based on the formulas for the geometric quantities originally derived by Funaki and rederived by the authors. The calculations for the surface area differ from those found earlier by Funaki.

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