scholarly journals The effect of nickel on secretory systems. Studies on the release of amylase, insulin and growth hormone

1974 ◽  
Vol 140 (2) ◽  
pp. 135-142 ◽  
Author(s):  
Robert L. Dormer ◽  
Alan L. Kerbey ◽  
Margaret McPherson ◽  
Susan Manley ◽  
Stephen J. H. Ashcroft ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Energy Metabolism ◽  
Cyclic Amp ◽  
Inhibitory Action ◽  
Substrate Oxidation ◽  
Tissue Concentrations ◽  
Mouse Pancreatic Islets ◽  
Stimulus Secretion Coupling ◽  
Potential Use ◽  
Systems Studies

The effects of Ni2+ on the release of amylase from rat parotids, insulin from mouse pancreatic islets and growth hormone from bovine pituitary slices were investigated. In all these secretory systems, Ni2+ was shown to inhibit release evoked by a variety of stimuli both physiological and pharmacological. Measurements of rates of substrate oxidation and tissue concentrations of ATP and 3′:5′-cyclic AMP suggest that this inhibitory action of Ni2+ does not arise through an effect on energy metabolism or cyclic AMP metabolism. It is concluded that although some effects of Ni2+ may involve antagonism between Ni2+ and Ca2+ in stimulus–secretion coupling, others appear to be independent of Ca2+. It is suggested that Ni2+ may block exocytosis by interfering with either secretory-granule migration or membrane fusion and microvillus formation. The possible mode of action of Ni2+ and its potential use as a tool in the study of exocytosis are discussed.

scholarly journals Requirement for adenosine triphosphate for stimulation in vivo of ox growth-hormone release

1974 ◽  
Vol 140 (3) ◽  
pp. 479-485 ◽  
Author(s):  
Margaret McPherson ◽  
J. George Schofield
Keyword(s):  
Growth Hormone ◽  
Cyclic Amp ◽  
Prostaglandin E2 ◽  
Adenosine Triphosphate ◽  
Hormone Release ◽  
Growth Hormone Release ◽  
Atp Content ◽  
Carbonyl Cyanide ◽  
Stimulus Secretion Coupling

Rotenone, carbonyl cyanide chloromethoxyphenylhydrazone and 2,4-dinitrophenol cause parallel falls in ox pituitary ATP content and growth-hormone release in the presence of 65mm-K+. Carbonyl cyanide chloromethoxyphenylhydrazone (0.4μg/ml) prevented the rise in growth-hormone release, but not the rise in 3′:5′-cyclic AMP content after addition of prostaglandin E2 (1μg/ml). The rate of hormone release from unstimulated slices and from slices in the presence of Ba2+ at 2.3 or 6.9mm was proportional to the ATP content of the slices. Carbonyl cyanide chloromethoxyphenylhydrazone at concentrations that inhibited release in the presence of the three secretagogues did not alter the pituitary contents of Na+, K+ or Ca2+. The implications of these observations are discussed in terms of the mechanism of stimulus–secretion coupling.

scholarly journals Brain-specific inhibition of mTORC1 eliminates side effects resulting from mTORC1 blockade in the periphery and reduces alcohol intake in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yann Ehinger ◽  
Ziyang Zhang ◽  
Khanhky Phamluong ◽  
Drishti Soneja ◽  
Kevan M. Shokat ◽  
...  
Keyword(s):  
Side Effects ◽  
Inhibitory Action ◽  
Alcohol Use Disorder ◽  
Alcohol Intake ◽  
Therapeutic Agents ◽  
Adverse Side Effects ◽  
Mtorc1 Activation ◽  
Potential Use ◽  
Heavy Alcohol Intake ◽  
Alcohol Dependent

AbstractAlcohol Use Disorder (AUD) affects a large portion of the population. Unfortunately, efficacious medications to treat the disease are limited. Studies in rodents suggest that mTORC1 plays a crucial role in mechanisms underlying phenotypes such as heavy alcohol intake, habit, and relapse. Thus, mTORC1 inhibitors, which are used in the clinic, are promising therapeutic agents to treat AUD. However, chronic inhibition of mTORC1 in the periphery produces undesirable side effects, which limit their potential use for the treatment of AUD. To overcome these limitations, we designed a binary drug strategy in which male mice were treated with the mTORC1 inhibitor RapaLink-1 together with a small molecule (RapaBlock) to protect mTORC1 activity in the periphery. We show that whereas RapaLink-1 administration blocked mTORC1 activation in the liver, RapaBlock abolished the inhibitory action of Rapalink-1. RapaBlock also prevented the adverse side effects produced by chronic inhibition of mTORC1. Importantly, co-administration of RapaLink-1 and RapaBlock inhibited alcohol-dependent mTORC1 activation in the nucleus accumbens and attenuated alcohol seeking and drinking.

scholarly journals Substrate oxidation in primary human skeletal muscle cells is influenced by donor age

2020 ◽  
Vol 382 (3) ◽  
pp. 599-608
Author(s):  
Vigdis Aas ◽  
G. Hege Thoresen ◽  
Arild C. Rustan ◽  
Jenny Lund
Keyword(s):  
Skeletal Muscle ◽  
Oleic Acid ◽  
Energy Metabolism ◽  
Substrate Oxidation ◽  
Pyruvate Dehydrogenase Kinase ◽  
Acid Oxidation ◽  
Acid Uptake ◽  
Donor Age ◽  
Human Myotubes ◽  
Human Skeletal Muscle Cells

AbstractPrimary human myotubes represent an alternative system to intact skeletal muscle for the study of human diseases related to changes in muscle energy metabolism. This work aimed to study if fatty acid and glucose metabolism in human myotubes in vitro were related to muscle of origin, donor gender, age, or body mass index (BMI). Myotubes from a total of 82 donors were established from three different skeletal muscles, i.e., musculus vastus lateralis, musculus obliquus internus abdominis, and musculi interspinales, and cellular energy metabolism was evaluated. Multiple linear regression analyses showed that donor age had a significant effect on glucose and oleic acid oxidation after correcting for gender, BMI, and muscle of origin. Donor BMI was the only significant contributor to cellular oleic acid uptake, whereas cellular glucose uptake did not rely on any of the variables examined. Despite the effect of age on substrate oxidation, cellular mRNA expression of pyruvate dehydrogenase kinase 4 (PDK4) and peroxisome proliferator–activated receptor gamma coactivator 1 alpha (PPARGC1A) did not correlate with donor age. In conclusion, donor age significantly impacts substrate oxidation in cultured human myotubes, whereas donor BMI affects cellular oleic acid uptake.

Possible role of cyclic GMP in stimulus-secretion coupling by salt gland of the duck

1979 ◽  
Vol 237 (5) ◽  
pp. C200-C204 ◽  
Author(s):  
D. J. Stewart ◽  
J. Sax ◽  
R. Funk ◽  
A. K. Sen
Keyword(s):  
Cyclic Amp ◽  
Guanylate Cyclase ◽  
Cyclic Gmp ◽  
Salt Gland ◽  
Domestic Ducks ◽  
Stimulus Secretion Coupling ◽  
Stimulation Of

Stimulation of salt galnd secretion in domestic ducks in vivo increased the cyclic GMP concentration of the tissue, but had no effect on cyclic AMP levels. Methacholine, which is known to stimulate sodium transport by the glands both in vivo and in vitro, stimulated ouabain-sensitive respiration in salt gland slices. Cyclic GMP stimulated ouabain-sensitive respiration to the same extent as methacholine. Guanylate cyclase stimulators, hydroxylamine and sodium azide, also stimulated ouabain-sensitive respiration. The stimulation of ouabain-sensitive respiration by methacholine was blocked either by atropine or by removal of calcium from the incubation medium. The stimulation of ouabain-sensitive respiration by cyclic GMP still occurred in the absence of calcium. The above observations seem to indicate that cyclic GMP acts as a tertiary link in the process of stimulus-secretion coupling in the tissue.

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