Tonin infused intravenously at a rate of 12 micron g/kg/min for 2 hours stimulated aldosterone and corticosterone secretion in conscious rats. In pentobarbital-anesthetized rats treated with dexamethasone and morphine, tonin stimulated aldosterone secretion, but corticosterone was unaffected. Tonin did not stimulate steroidogenesis in isolated rat adrenal glomerulosa cells unless substrate, in the form of "stripped" rat plasma, was added, in which case large amounts of immunoreactive angiotensin II were generated. These results suggest that tonin may generate an angiotensin peptide in vivo, which in turn stimulates aldosterone secretion. ACTH is secreted in response to tonin infusion, and contributes to the adrenal response.

Adrenal Glands↗

PubMedDate not supplied

[Acute alcoholic intoxication by the percutaneous route. Clinical and experimental study].

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Acute Disease↗

PubMedDate not supplied

Relative roles of sodium and calcium ions in the steroidogenic response of isolated rate adrenal glomerulosa cells.

To study the relative roles of sodium (Na+) and calcium ions (Ca2+) in the response of adrenal glomerulosa cells, we investigated the effects of different Na+ concentrations in the incubation media and the actions of substances that interfere with Ca2+ fluxes. Basal aldosterone secretion and response to angiotensin II (AII), adrenocorticotropic hormone (ACTH), or potassium (K+) were dependent on extracellular Na+ concentration. Veratridine, a Na+ channel opener that dissipates Na+ gradients, blocked the stimulated steroidogenic response. Mersalyl acid and tetracaine, which are potent Ca2+ antagonists, blocked the effects of aldosterone secretagogues. Divalent cations with Ca2+ antagonistic action such as manganese M(n2+), nickel (Ni2+), and cobalt (Co2+) blocked the aldosterone secretory response to AII, ACTH, and K+. Barium (Ba2+) and strontium (Sr2+), known to mimick Ca2+ effects, increased or did not affect responses of the glomerulosa cells. Sodium vanadate, an inhibitor of ATP-dependent Ca2+ translocation, did not alter the stimulated aldosterone responses. Trifluoperazine (10(-6) M), an inhibitor of calmodulin, blocked AII and K+-induced aldosterone secretion, but was partially effective on ACTH-stimulated aldosterone output only at a concentration of 10(-5) M. The actions of ouabain on aldosterone biosynthesis were similarly affected by all these drugs. Thus, both extracellular Na+ and Ca2+ appear to play a role in the steroidogenic response of isolated glomerulosa cells. The intracellular action of Ca2+ may involve a calmodulin-like protein. The effects of ACTH are only partially dependent on Ca2+ as a second intracellular messenger.

Adrenal Cortex↗

PubMedDate not supplied

Effect of serum amyloid A, HDL-apolipoprotein, on endothelial cell proliferation. Implication of an enigmatic protein to atherosclerosis.

The possible contribution of apo-HDL serum amyloid A (SAA) to the protective effect of HDL against atherosclerosis was studied by evaluating its effect on bovine aortic endothelial cell (BAEC) proliferation. Our results suggest that human SAA, both purified and recombinant, in concentrations relevant to mild acute phase events, significantly inhibit endothelial cell proliferation in a dose-dependent manner (e.g., 50 micrograms/ml causes approximately 88% inhibition; p < 0.001). This inhibition was attenuated by addition of fibroblast growth factor (FGF), which antagonized the SAA-mediated effect. As levels of TNF may be highly elevated during the acute phase response, its effect on BAEC proliferation was evaluated and found, at concentrations of > 1 pg/ml, to be substantially inhibitory Co-incubation of cells with both SAA and TNF was inhibitory, albeit neither additive nor synergistic. FGF antagonized the effect of both proteins. Amyloidic deposit (AA, i.e. SAA 1-76), derived from pathological proteolysis of SAA, practically retains the inhibitory activity (e.g. 50 micrograms/ml causes approximately 66% inhibition; p < 0.001) but apparently lacks the regulatory site towards FGF. In contrast to the above inhibitory effect, synthetic SAA-related peptide corresponding to the sequence 29-33 of SAA enhances BAEC proliferation (50 micrograms/ml causes approximately 64% increase; p < 0.001). The present data, coupled with our previous observations in which SAA was found to induce endothelial PGI2 formation and to inhibit overproduction of PGI2 by TNF and LPS as well as platelet aggregation, may suggest that SAA contributes to the protective effect of HDL against atherosclerosis. This, by means of its modulatory effect on endothelial cell and platelet activation, primarily in the presence of other regulatory proteins. SAA-derived peptides may, potentially, be used as therapeutic agents in the treatment of atherosclerosis and cardiovascular diseases.

Amino Acid Sequence↗

PubMedDate not supplied

Modulation of prostaglandin I2 production from bovine aortic endothelial cells by serum amyloid A and its N-terminal tetradecapeptide.

The study was aimed to explore the possible involvement of the acute phase HDL apolipoprotein, serum amyloid A (SAA) in the regulation of PGI2 production by endothelial cells. This, in view of the recent detection of SAA mRNA in endothelial cells of human atherosclerotic lesions. Human SAA induces PGI2 formation in bovine aortic endothelial cells culture in a concentration relevant to moderate acute phase events. 50 micrograms/ml of purified human SAA increases PGI2 production from a mean basal level of 2,490 +/- 330 pg/ml by 1.80 +/- 0.1 fold (n = 10; p < 0.01). The PGI2 inducing activity resides apparently in the N-terminal, i.e. amino acid residues 1-14, of the SAA molecule, 50 micrograms/ml of the peptide induces 2.9 +/- 0.5 fold increase of PGI2 production (n = 4; p < 0.03). TNF and LPS each induce PGI2 production in a concentration and time dependent manner. TNF in concentration of 10 ng/ml induces, in the presence of calf serum, an increase of 24.9 +/- 2.3 fold (n = 4; p < 0.001) and LPS in concentration of 1 microgram/ml causes a 18.3 +/- 1.3 fold increase, (n = 4; p < 0.01). In serum-free cultures, only a 2.5 +/- 0.3 fold increase was detected by 10 ng/ml TNF (n = 4), and a 5.9 +/- 0.4 by 1 microgram/ml of LPS. Thus, serum has a strong effect on PGI2 induction. When 50 micrograms/ml SAA is coadministered with 1 ng/ml TNF it reduces the TNF-induction of PGI2 from 7.7 +/- 2.8 to 3.3 +/- 1.2 fold (n = 4; p < 0.01). SAA attenuates, as well, LPS-mediated activity, although in a less pronounced manner. Our finding suggest a potential physiological function for SAA in regulation of basal and cytokine-induced PGI2 production by vascular endothelium. The capacity of SAA to markedly moderate PGI2 induction by TNF and LPS suggest that it may play a role in defending against vessel damage, in cases of atherosclerosis, bacterial infection or septic shock. The induction of PGI2 by SAA through its N-terminal domain, which also exhibits an anti-platelet aggregation activity, suggests a potential therapeutical use for this peptide as an anti-hypertensive and an anti-aggregatory agent.

Amino Acid Sequence↗