Acceptance of L-glutamate as an excitatory transmitter was relatively slow compared to other transmitters, such as GABA. However, the transmitter role of L- glutamate has received more attention recently. In the crustacean neuromuscular junction L-glutamate fulfills most of the criteria for the transmitter identification. Studies on the glutamate receptor antagonist suggest that L-glutamate may also be the transmitter at the squid giant synapse. L-Glutamate may be the excitatory transmitter in many parts of CNS, although the evidence for this hypothesis is still not complete. The role of L-aspartate as the transmitter in CNS is not clear but its contribution may be less than that of L-glutamate. Glutamate receptors have been classified into three groups according to pharmacological properties. However, recent observations suggest that the situation seems more complicated than previously expected and more detailed comparison between synaptic potentials and glutamate action is needed.

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The effects of Intraventricular bombesin (BS) at doses of 0.1, 1.0, and 10.0μg on thermoregulatory and cardiovascular functions were studied in conscious rats with a direct calorimeter at ambient temperatures (T_a) of 18, 23, and 28°C. At two lower T_as, the central BS produced a profound decrease in colonic temperature (T_col) with a reduction of the temperature difference between the interscapular brown adipose tissue (BAT) and the colon (T_BAT-T_col). Increases in nonevaporative and evaporative heat losses and mean arterial blood pressure (BP) were consistent following the central BS at any dose tested at any T_a. In the sinoaortic deafferentated rats, a 0.1μg of BS produced hypothermia with a significant decrease in (T_BAT-T_col) and heat production (M). Changes in T_col, (T_BAT-T_col), and M in the denervated rats, however, were not different from those in the sham-operated rats. These results suggest that the central BS suppresses BAT thermogenesis and facilitates heat loss mechanisms. The baroreflex-mediated metabolic reduction is not the case in the BS-induced hypothermia in rats.

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In examining the relation between the maximum upstroke velocity of the action potential (V_max) and available Na conductance (ag_Na), the dose-response curve for tetrodotoxin (TTX) and the steady-state inactivation (h_∞)-membrane potential curve were obtained by measuring Na current (I_Na) as well as V_max in single isolated frog ventricular cells. The present experiment demonstrated that the relation between V_max and ag_Na is linear. On the other hand, simulation analysis of this relation in the absence of leakage current (I_L), in which the necessary parameters for I_Na had been determined by the voltage clamp experiment, showed non-linear properties. The non-linear relation originates from the fact that kinetic variable, m, and driving force for I_Na at the time of V_max is not constant with respect to the change in either h₀ or g_Na. A reasonable explanation for this discrepancy is that the presence of I_L suppresses the total ionic current at the time of V_max and hence the change in I_Na does not straightforwardly reflect that in V_max.

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Noradrenaline (NA) turnover of the interscapular brown adipose tissue (BAT) was determined in order to evaluate a role of sympathetic NA of this tissue in an enhanced nonshivering thermogenesis which had been previously evidenced in the repetitively stressed rats by immobilization (daily 3-h immobilization for 4 weeks) and the coldacclimated ones (5°C, 4 weeks). The disappearance rate of NA from the BAT following blockade of NA synthesis with α-methyl p-tyrosine was adopted for estimation of NA turnover of the tissue. Cold acclimation increased both fractional turnover rate (%/h) (k) and turnover rate (ng/(g BAT•h)). Repetitive immobilization stress also elevated turnover rate, but not k. In the warm non-stressed controls acute cold exposure to -5°C and acute immobilization stress elevated the turnover rate. The effect of cold exposure was significantly greater than that of immobilization stress for both indices of NA turnover. In the cold-acclimated rats acute cold exposure increased k as well as turnover rate, but not acute immobilization stress. In the repetitively immobilized rats both acute cold exposure and acute immobilization stress elevated k and turnover rate. These results indicate that immobilization enhances sympathetic activity of thermogenic tissue, BAT. The results also suggest that the extent of sympathetic participation is not necessarily the same between the cold-acclimated and the stressed rats.

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The design and properties of thermal detectors constructed with multiple layers of polyvinylidene fluoride film are described. By use of these detectors, production of heat by the photoreceptors in the darkadapted bullfrog retina in response to brief pulses of very weak light was examined. In response to brief light pulses delivering an average of 1 photon per retinal rod, the retina was found to produce heat more-or-less abruptly after a latent period of 0.2 to 0.4s. At this level of pulse intensity, the thermal energy produced by the retina was approximately 1, 500, 000 times as large as the total radiant energy delivered to the retina for stimulation. It appears possible that a large number of disks in the rod outer segment are activated by absorption of a single photon.

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The mechanisms involved in the long-lasting contraction induced by transmural stimulation were investigated in the isolated longitudinal muscle of the guinea-pig gastric corpus. Transmural stimulation induced an initial rapid contraction, a subsequent relaxation and a long-lasting contraction which was mimicked closely by the responses to noradrenaline and ATP. The rapid contraction was blocked by tetrodotoxin or by atropine, and the subsequent relaxation was also blocked by tetrodotoxin, but not by atropine. The long-lasting contractions were not inhibited by atropine, phentolamine, and propranolol. However, some of those were partially inhibited by tetrodotoxin and guanethidine, and others were enhanced by tetrodotoxin. The noradrenaline- but not ATP-induced long-lasting contraction was blocked by phentolamine. Furthermore, indomethacin completely abolished the long-lasting contractions induced by transmural stimulation, noradrenaline, and ATP, but did not significantly affect the response to prostaglandin E₂. The results indicate that the long-lasting contraction induced by transmural stimulation is mediated through prostaglandins release which may be triggered by neuro-transmitters or by endogenous substances.

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The effects of vasopressin, angiotensin II, and calcium ionophore A23187 were examined and compared on endogenous prostaglandin E₂ (PGE₂) production, in the absence of exogenous arachidonate, by glomeruli and cortical and medullary collecting tubules freshly prepared from rat kidney. Angiotensin II stimulated PGE₂ production in the glomeruli but not in the collecting tubules. Vasopressin at concentrations which stimulate cAMP production in collecting tubules failed to stimulate PGE₂ production in both glomeruli and collecting tubules. Significant stimulation of PGE₂ production occurred in response to calcium ionophore A23187 in both glomeruli and collecting tubules. These results showed that vasopressin failed to stimulate PGE₂ production from endogenous precursors in both glomeruli and collecting tubules of the rat kidney while angiotensin II stimulates PGE₂ production in the glomeruli but not in collecting tubules. In addition, an ability to produce PGE₂ may be greater in medullary than in the cortical portions of collecting tubules as judged by the response to calcium ionophore.

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The rabbit adrenal gland was perfused with a modified Locke's medium and the mechanism of adrenaline secretion induced by nitrophenol compound was investigated. The secretory response to 2, 4-dinitrophenol (DNP) or trinitrophenol (TNP) showed the following peculiar features. (1) Prolonged exposure to DNP or TNP caused an immediate, and long-lasting increase of secretion only in the presence of Ca. (2) The response to DNP depended on the concentration of Ca, but that to TNP was largest in the presence of 0.5mM Ca. (3) Re-addition of 2mM Ca during prolonged exposure to DNP or TNP produced a larger response than did the simultaneous addition of Ca and either DNP or TNP. (4) The response to DNP in the presence of 2mM Ca was markedly reduced by removal of external Na, but the Na dependency became less marked in the presence of 0.1mM Ca. The response to TNP in the presence of 0.5mM Ca was slightly reduced in the absence of Na. (5) DNP or TNP caused a much larger response during depolarization with a high K, Rb, or Cs medium than that with a 5mM KCl medium. (6) The response to DNP was largely potentiated in the absence of most ions in the presence of only 0.1mM Ca and that to TNP was potentiated in the presence of only 0.5mM Ca under the same condition. (7) Re-addition of Ca 5min after the removal of DNP or TNP still caused substantial secretion. These results suggest that nitrophenol compounds stimulate secretion by two independent mechanisms: one is related to its effect on the surface potentials of the plasma membrane and the other unknown except for the possible dependence of Na and Ca.

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Although the pressure-rate product (double product; DP) is generally recognized as a good index of myocardial oxygen consumption (V_O2), catecholamines are reported to change the V_O2-DP relationship. However, the separate influences of chronotropism and inotropism on the V_O2-DP relation have not been studied. Therefore, we examined these influences in anesthetized open-chest dogs by cardiac pacing and dobutamine infusion. We observed two different V_O2-DP lines under the separate chronotropic and inotropic changes. We interpreted such V_O2-DP relations by the concept of the pressure-volume area (PVA). PVA is a measure of total mechanical energy for ventricular contraction and is a specific area in the ventricular pressure-volume (P-V) diagram circumscribed by the end-systolic and end-diastolic P-V relation curves and the systolic segment of the P-V trajectory. The empirical V_O2-PVA relation that had been obtained in our previous studies reasonably simulated the dissociation of DP from V_O2 under separate changes in chronotropism and inotropism.

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In chloralose anesthetized dogs and decerebrated dogs whose pyloric sphincter was submucosally ligated, the pancreatic exocrine secretory response to antral distension was studied. Distensions of the antral pouch with Tyrode's solution and 0.1N HCl caused graded rises in pancreatic flow and protein and bicarbonate outputs. The serum gastrin concentration gradually rose after the distension with Tyrode's solution, while no rise in serum gastrin was elicited by acid distension. After cervical vagotomy, a reduced pancreatic response persisted but no rise in the serum gastrin was seen. After splanchnicectomy following vagotomy, the pancreatic response became greater than before splanchnicectomy. This pancreatic response was observed even after caeliac and superior mesenteric ganglionectomies, but was completely abolished by an external tight ligature around the pyloric sphincter, or by administration of hexamethonium or atropine sulfate. The results suggest the existence of an antro-pancreatic short reflex in addition to a long route vago-vagal reflex.

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Changes in hematocrit and plasma oncotic pressure were measured continuously during and after isotonic volume expansion in splenectomized dogs in order to test the potential of these types of measurements to predict changes in plasma volume. A volume of Ringer's solution amounting to 15% of the initial blood volume was infused over 10min. At the end of the infusion, 54% of infused fluid remained within the intravascular space and 9% of the infused volume was retained within the intravascular space at 50min after the end of the infusion. Hematocrit and plasma oncotic pressure decreased by 2.4% and 2.4mmHg, respectively, at the end of infusion and then variables returned to their control levels gradually. Changes in plasma volume were estimated indirectly from hematocrit and plasma oncotic pressure based on the dilution of the erythrocytes and the protein. Highly significant correlations were observed between the measured plasma volume (Y) and the plasma volume (X) calculated from hematocrit (Y=0.95X+0.22, r=0.96) and the plasma oncotic pressure (Y=0.86X+0.46, r=0.91). We therefore conclude that either hematocrit and plasma oncotic pressure measured continuously are reliable parameters for predicting the time course of the plasma volume change during an isotonic volume expansion of up to 15% of the initial blood volume.

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The influence of esophageal (T_es) and skin temperature (T_sk) variations, body heat storage, and individual parameters on the initiation of sweating was investigated in 9 unacclimated subjects during thermal transients induced by exercise (25, 50, or 75W) and by a step change in ambient temperature from 28°C to 23, 28, 36.5, 45, or 50°C. Seventy-four onsets of sweating were observed during the exposures, the sweating delay averaging 3min at 45 and 50°C, 6min at 36.5°C, and 9.5min at 28°C. In warm conditions (36.5 to 50°C), the onset of sweating could mainly be related both to the level of T_sk and its rate component, whereas in cooler conditions (28 and 23°C), the onset of sweating could only be related to a positive rate of T_es variation, the T_sk level being low and steady. On the whole set of data, the T_es changes at the onset were inversely related to the T_sk changes. The cumulated heat storage at the onset of sweating was 37kJ/m² (S.D. 25). It varied not only among subjects (range: 11-66kJ/m²) but also within subjects even when differences in thermal state prior to exercise were accounted for. Among the individual parameters investigated, the magnitude of the decrease in T_es observed in response to the start of exercise was found to have a significant effect on the sweating delay. The T_es decrease was inversely related to the subject's skinfold thickness, and in a given subject, inversely related to the preexercise T_sk. It is concluded that the results are in agreement with a summation model of internal and mean skin temperatures on the sweating drive but that they do not verify the hypothesis of a critical level of heat storage at the onset of sweating.

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The effects of both exercise training and intermittent cold acclimation on heat production (shivering and nonshivering thermogenesis (NST)) in rats were studied. Warm-acclimated rats (housed at 24°C, WA) and intermittently cold-acclimated rats (exposed daily to -5°C for 2h, CA) were forced to run (25m•min-1 for 1h) every day (WA-T and CA-T). WA and CA left sedentary (WA-S and CA-S) served as controls. Norepinephrine (NE)-induced thermogenic capacity assessed from the increment of oxygen consumption (V_O2) and colonic temperature (T_c) were measured 4 weeks after commencing acclimation and exercise training. The thermogenic capacity was greater in CA than in WA. However, in WA, WA-T responded to NE less than WA-S, whereas the response of CA-T and CA-S did not differ. Wet weight of interscapular brown adipose tissue (IBAT) and its protein (and dry matter-regarded to be highly representative of protein) content were larger in CA than in WA. Respective sedentary and exercised groups of rats had similar IBAT protein (and dry matter) content although tissue weight was lighter in WA-T than in WA-S. Lipid content of IBAT was also larger in CA than in WA. IBAT of WA-T had less lipid compared to that of WA-S while no difference was seen between CA-S and CA-T. Shivering activity during acute cold (4°C) exposure was less in CA compared to WA and there was no difference between respective groups of exercised and sedentary rats. Propranolol, a blocker of NE-dependent NST, eliminated the difference in shivering among these four groups. When exposed to severe cold (-10 or -20°C), the fall in T_c of rats fasted for 18h was greater in WA than in CA. CA-T showed a greater decrease in T_c than CA-S during -20°C exposure while it did not differ during -10°C exposure. On the other hand, T_c of WA-T and WA-S did not differ significantly during either cold exposure period. These results suggest that exercise training in rats housed at 24°C suppresses NE-dependent NST whereas another nonshivering thermogenic mechanism (NE-independent) fray compensate this suppression. However, NE-dependent NST of WA-S and WA-T did not parallel protein (dry matter) content of IBAT; no difference existed in IBAT protein between these two groups. Our results also show that exercise training: i) does not suppress NE-dependent NST in CA and ii) does not affect maximal shivering activity of WA and CA.

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The effect of water ingestion on bile secretion was investigated in nine cholecystectomised patients with T-tube biliary drainage. The effect of ingestion of a standard meal on bile secretion was also studied in these patients. Water ingestion produced a significant increase in bile secretion compared with fasting levels. This increase in bile secretion was comparable to that produced by a standard meal. Ingestion of water or meal did not produce any significant change in bile osmolality or sodium and potassium concentrations of bile.

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We investigated the hypothesis that ketamine-induced respiratory depression might be mediated through the opiate system that can be eliminated by naloxone. The steady-state respiratory responses to iv. ketamine (2mg•ml^-1•kg^-1) and their antagonism by naloxone (0.4mg•ml^-1•kg^-1) were studied in anesthetized, paralyzed, vagotomized, and artificially ventilated cats. We found that ketamine depressed central respiratory output, assessed from the phrenic nerve electroneurogram, leading to apneustic breathing, which was not antagonized by naloxone. The apneustic respiratory depression by ketamine was thus mediated through mechanism other than the opiate system.

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To study the types of the monocular eye movements, intracortical microstimulations were applied to the fundus of the cat's coronal sulcus where the monocular movements of the contralateral eye were evoked. The monocular eye movements were saccadic and directed toward the nasal side converging on a horizontal line from various eye positions. The average threshold and latency were 18.0μA (range 8-30μA) and 19.5ms (range 18-20ms), respectively.

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Effects of acute cold exposure (10°C for 60min) on the concentrations of adrenocorticotropin (ACTH) and zinc in plasma were investigated in seven healthy male students. There were no significant changes in total zinc, albumin-bound zinc, and α₂-macroglobulin-bound zinc concentrations throughout the experimental period. On the other hand, ACTH concentration increased markedly during cold exposure. In addition, a statistically significant inverse relationship existed between the changes in ACTH and albumin-bound zinc values during the experiment. These results suggest that acute cold exposure produces elevated plasma ACTH levels, with resulting zinc redistribution in the human body.

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For inspective determination of blood pressure at rest and during exercise, simultaneous recordings of cuff pressure, Korotkov's sounds, and ECG by an electromagnetic oscillograph were necessary. We devised an apparatus in line with the requirement. Results obtained using this apparatus demonstrate that the auscultatory recording method is suitable to determine the blood pressure during submaximal bicycle exercise.

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