Differential action of hepatic sympathetic neuropeptides: metabolic action of galanin, vascular action of NPY

Activation of hepatic nerves increases both hepatic glucose production (HGP) and hepatic arterial vasoconstriction, the latter best described by a decrease of hepatic arterial conductance (HAC). Because activation of canine hepatic nerves releases the neuropeptides galanin and neuropeptide Y (NPY) as well as the classical neurotransmitter norepinephrine (NE), we sought to determine the relative role of these neuropeptides vs. norepinephrine in mediating metabolic and vascular responses of the liver. We studied the effects of local exogenous infusions of galanin and NPY on HGP and HAC to predict the metabolic and vascular function of endogenously released neuropeptide. Galanin (n = 8) or NPY (n = 4) was infused with and without NE directly into the common hepatic artery of halothane-anesthetized dogs, and we measured changes in HGP and HAC. A low dose of exogenous galanin infused directly into the hepatic artery potentiated the HGP response to NE yet had little effect on HGP when infused alone. The same dose of galanin infused into a peripheral vein (n = 8) did not potentiate the HGP response to NE, suggesting that the locally infused galanin acted directly on the liver to modulate NE's metabolic action. In contrast, a large dose of exogenous NPY failed to influence HGP when infused either alone or in combination with NE. Finally, NPY, but not galanin, tended to decrease HAC when infused alone; neither neuropeptide potentiated the HAC response to NE. Therefore, both hepatic neuropeptides may contribute to the action of sympathetic nerves on liver metabolism and blood flow. It is likely that endogenous hepatic galanin acts directly on the liver to selectively modulate norepinephrine's metabolic action, whereas endogenous hepatic NPY acts independently of NE to cause vasoconstriction.     

Inspection of human salivary alpha-amylase action by its transglycosylation action

The course of the action of human salivary alpha-amylase (HSA) on a substrate was examined taking advantage of its transglycosylation action. IG5 phi (IG-G-G-G-G-phi), IG4 phi (IG-G-G-G-phi), and GIG4 phi (G-IG-G-G-G-phi) were used as the substrates and p-nitrophenyl alpha-glucoside (GP, G-P) as the acceptor. HSA hydrolyzes IG5 phi, IG4 phi, and GIG4 phi to IG3 (IG-G-G) and G2 phi (G-G-phi), to IG3 and G phi (G-phi), and to GIG3 (G-IG-G-G) and G phi, respectively. In the presence of GP, a part of the glycon residues, IG3 and GIG3, were transferred to the acceptor to give IG4P (IG-G-G-G-P) and GIG4P (G-IG-G-G-G-P), respectively. Whenever the enzyme attacks the substrate, G phi or G2 phi is liberated in both transglycosylation and hydrolysis. The extent of transglycosylation can be, therefore, estimated from the molar ratio of the transfer product to the liberated aglycon, G phi or G2 phi. HPLC analysis of the reaction mixtures revealed that the value of IG4P/G phi in the digest of IG4 phi was nearly equal to that of GIG4P/G phi in the digest of GIG4 phi and these values were ten times larger than that of IG4P/G2 phi in the digest of IG5 phi. These data suggested that G phi residue would fall away from aglycon binding site more rapidly than G2 phi residue after the cleavage of the alpha-1,4-glycosidic linkage to offer GP more chance to attack to the activated glycon and also indicated that the space of the glycon binding site corresponds to three glucose residues.     

Lymphocyte-increasing action and hypocalcemic action of parotid gland extract.

It has previously been shown in our laboratory that the hypocalcemic substances purified from the thymus have a potent lymphocyte-increasing action in mice. Then, lymphocyte-increasing activity was examined with bovine parotid gland extracts, which showed a hypocalcemic activity as potent as that of the thymus extracts. The lymphocyte-increasing activity was assayed in the littermates of neonatal mice of Swiss-Webster strain; the materials used for this experiment were purified preparations and several fractions obtained from the parotid gland extracts in the course of purification. It was found that the potency of lymphocyte-increasing activity rose approximately in parallel with the rise in hypocalcemic activity with progress in purification. The final product, which was purified from the gland by isoelectric precipitation at pH 5.4, fractional precipitation with ammonium sulfate, chromatography on DEAE-cellulose, gel filtration on Sepharose 6B and preparative disc electrophoresis, gave a single band in polyacrylamide gel electrophoresis. Its intravenous injection in rabbits, in a dose of 10 mug/kg, produced a significant lowering in serum calcium (percent decrease 10.24 +/- 1.06%) compared with control animals given an injection of physiological saline. Intraperitoneal injection of this purified product, in a dose of 0.5 mug/mouse, in the littermates of neonatal mice, also produced a significant increase (ratio of lymphocytes to polymorphs 2.47 +/- 0.07) in lymphocytes compared with control animals injected with physiological saline (L/P ratio 1.57 +/- 0.05). These facts suggest that this purified protein fraction inherently contains both activities, but the possibility cannot be ruled out of slight contamination by a substance having a high activity. On the other hand, a fraction having no activity for lowering serum calcium but which had activity for increasing the lymphocytes was obtained. This is the first paper to report the presence of lymphocyte-increasing substances in the bovine parotid gland and the purification of one of the substances from the gland.     

Mineralocorticoid action

The physiology of mineralocorticoid action, particularly with respect to epithelial sodium transport, is well defined. A full understanding of the molecular basis of mineralocorticoid action has however proven to be more elusive. In the last decade insights into structural and functional aspects of the mineralocorticoid receptor combined with emerging details of the components of the mediators of the sodium flux has resulted in a clearer picture. This review focuses on two aspects of these new developments; the mineralocorticoid receptor and putative aldosterone induced proteins.     

Investigating action understanding: inferential processes versus action simulation

In our daily life, we continuously monitor others' behaviors and interpret them in terms of goals, intentions, and reasons. Despite their central importance for predicting and interpreting each other's actions, the functional mechanisms and neural circuits involved in action understanding remain highly controversial. Two alternative accounts have been advanced. Simulation theory assumes that we understand actions by simulating the observed behavior through a direct matching process that activates the mirror-neuron circuit. The alternative interpretive account assumes that action understanding is based on specialized inferential processes activating brain areas with no mirror properties. Although both approaches recognize the central role of contextual information in specifying action intentions, their respective accounts of this process differ in significant respects. Here, we investigated the role of context in action understanding by using functional brain imaging while participants observed an unusual action in implausible versus plausible contexts. We show that brain areas that are part of a network involved in inferential interpretive processes of rationalization and mentalization but that lack mirror properties are more active when the action occurs in an implausible context. However, no differential activation was found in the mirror network. Our findings support the assumption that action understanding in novel situations is primarily mediated by an inferential interpretive system rather than the mirror system.     

Direct action of estradiol-17β on the atrial action potential

The effect of the two C-17 isomers of estradiol on the shape of the action potential of rat atrial tissue was studied by means of classical glass electrodes for different concentrations of estradiol. Resting potential and upstroke were not affected by estradiol, but the duration of the action potential was reduced. Only estradiol-17β exhibits an effect in a concentration dependent way, while estradiol-17α has no effect at all. The ionic mechanism was studied by adding specific ionic blockers to the perfusate. Since the effect was much less pronounced when a slow inward current blocker was added, it was concluded that estradiol-17β acts mainly via the slow inward current channel. Only a small part of the interaction takes place via the potassium outward channel.     

The action of locustol

Bioassays have shown that the locust gregarization pheromone, locustol, and the adrenergic hormone, noradrenaline, act in a similar way on the phase characteristics of the locust and are thus mimics. Investigations of the affects of dopa (a noradrenaline substrate) and its antagonist aldomet, and of the effects of adenosine 3′–5′ monophosphate (cyclic AMP), its agonists and antagonists, as well as an assay of cyclic AMP in the two phases, have strengthened this conclusion. It is postulated that the pheromone acts like an adrenergic hormone to promote the production of cyclic AMP which effects the characteristic changes when the solitary phase of locusts transforms into the gregarious phase.