Electrophilic and Drug-Induced Stimulation of NOTCH3 N-terminal Fragment Oligomerization in Cerebrovascular Pathology

Author(s):  
K. Z. Young ◽  
N. M. P. Cartee ◽  
S. J. Lee ◽  
S. G. Keep ◽  
M. I. Ivanova ◽  
...  
The Lancet ◽  
1964 ◽  
Vol 283 (7347) ◽  
pp. 1368-1369 ◽  
Author(s):  
Phillip Holland ◽  
AlvinM. Mauer

1957 ◽  
Vol 190 (2) ◽  
pp. 350-355 ◽  
Author(s):  
Edgar Haber ◽  
Kurt W. Kohn ◽  
S. H. Ngai ◽  
D. A. Holaday ◽  
S. C. Wang

Medulla oblongata of 80 vagotomized cats was explored with microelectrodes. Spontaneous respiratory neuronal activities and chest movements were recorded simultaneously with a twin beam cathode ray oscilloscope. It was found that inspiratory discharges are concentrated in the reticular formation between 3 mm rostral and 1 mm caudal to the level of the obex, which corresponds approximately to the inspiratory region of Pitts, Magoun and Ranson. On the other hand, expiratory discharges are not obtained in Pitts' expiratory area, but are found in a circumscribed region in the reticular formation from the level of the obex to 3 mm caudally. Electric stimulation of this region has been found recently by Ngai and Wang to yield marked expiratory spasm. It is concluded that the expiratory center is located caudally to the inspiratory center in the cat. The spontaneous respiratory neuronal discharges continue with no alterations of pattern of firing during drug-induced respiratory paralysis, and are increased both in number and in frequency during CO2 inhalation. Stimulation of the vagus nerve with 50 shocks/sec. reduces inspiratory discharges and prolongs the duration of expiratory discharges.


1962 ◽  
Vol 202 (5) ◽  
pp. 984-986 ◽  
Author(s):  
Mary J. Pohala ◽  
C. Y. Yen ◽  
Heron O. Singher

Neuroactive drugs were investigated for their ability to produce a blood plasma fibrinolysin in experimental animals. Following intravenous injections of these drugs, blood samples were drawn and the plasma studied for fibrinolytic activity as indicated by the Astrup fibrin plate technique. Drugs inducing a small degree of fibrinolytic activity in dogs were acetylcholine hydrochloride, epinephrine hydrochloride, carbamylcholine chloride, physostigmine salicylate and prostigmine methylsulfate. The possible mechanism of drug-induced fibrinolysin as compared with the biological activation of profibrinolysin is interpreted on the basis of stimulation and release of catecholamines resulting from stimulation of sympathetic ganglia and the adrenal medulla.


Endocrinology ◽  
2009 ◽  
Vol 150 (8) ◽  
pp. 3766-3773 ◽  
Author(s):  
Ping Tai ◽  
Koji Shiraishi ◽  
Mario Ascoli

We used proliferating primary cultures of immature rat Leydig cells expressing the recombinant human LH/choriogonadotropin (CG) receptor (LHR) to test the hypothesis that activation of this receptor inhibits apoptosis. We also compared the effects of LH/CG with epidermal growth factor (EGF) and IGF-I because these have been previously shown to stimulate proliferation and/or inhibit apoptosis in Leydig cells. Human CG (hCG), EGF, and IGF-I stimulated the phosphorylation of ERK1/2 and Akt in primary cultures of immature rat Leydig cells. These three hormones also robustly stimulated thymidine incorporation and inhibited drug-induced apoptosis. Using selective inhibitors of ERK1/2 (UO126) or Akt phosphorylation (LY294002), we show that the ERK1/2 and Akt cascades are both involved in the hCG- and EGF-dependent proliferation of Leydig cells, but only the ERK1/2 cascade is involved in their antiapoptotic actions. The same strategy showed that the proliferative and antiapoptotic actions of IGF-I are mediated entirely by the Akt pathway. These results show that activation of the LHR inhibits apoptosis in Leydig cells and that it does so through stimulation of the ERK1/2 pathway.


1997 ◽  
Vol 4 (5-6) ◽  
pp. 244-249 ◽  
Author(s):  
Helena Haberstock-Debic ◽  
Hrvoje Banfic ◽  
Wim J. Stevens ◽  
Luc S. De Clerck ◽  
Eleonora Wechsung ◽  
...  

1987 ◽  
Vol 115 (3) ◽  
pp. 505-510 ◽  
Author(s):  
N. M. Wulffraat ◽  
H. A. Drexhage ◽  
P. Jeucken ◽  
R. D. van der Gaag ◽  
W. M. Wiersinga

ABSTRACT Stimulation of adrenal DNA synthesis by ACTH(1–39) and its fragments ACTH(1–24) (Synacthen) and ACTH(18–39) was investigated. Synthesis of DNA was measured as the increase in the percentage of cells in S-phase (Feulgen densitometry) in guinea-pig adrenal explants kept in organ culture and exposed to the peptides for 5 h at 37 °C. ACTH(1–39) and its C-terminal fragment ACTH(18–39) (corticotrophin-like intermediate lobe peptide) were found to be potent stimulators of in-vitro adrenal DNA synthesis. The dose–response kinetics were biphasic and optimal responsiveness was reached in both instances at 1 fmol/1–10 pmol/l (this biological effect of ACTH(18–39) has hitherto not been described). The N-terminal fragment ACTH(1–24) gave only minimal responses. Thyrotrophin and LH, tested as controls, did not induce adrenal DNA synthesis. Epidermal growth factor was a potent stimulator of adrenal DNA synthesis in vitro. Our data suggest a trophic action of the C-terminal part (ACTH(18–39)) of the corticotrophic molecule. Clear trophic effects were also found for the N-terminal part of the pro-opiomelanocortin molecule N-POC(1–76) (optimum 0·1 nmol/l) and N-POC(51– 62) (optimum 0·1 pmol/l). The latter observations support earlier concepts that this part of the proopiomelanocortin molecule has a stimulatory effect on adrenal DNA synthesis. J. Endocr. (1987) 115, 505–510


1988 ◽  
Vol 256 (3) ◽  
pp. 733-739 ◽  
Author(s):  
V Shoshan-Barmatz

Preincubation of sarcoplasmic reticulum (SR) with propranolol or tetracaine inhibits Ca2+ accumulation and stimulates ATPase activity by more than 2-fold. This effect is obtained only when the preincubation is carried out in the presence of ATP or other nucleoside triphosphates. The (ATP + drug)-induced inhibition of Ca2+ accumulation is pH-dependent, increasing as the pH rises above 7.5. The presence of micromolar concentrations of Ca2+ or Mg2+ during the preincubation prevents the inhibitory effect of ATP plus drug on Ca2+ accumulation or ATPase activity. The (ATP + drug) modification of SR vesicles resulted in stimulation of a rapid Ca2+ efflux from passively loaded vesicles. The ATP-dependent inhibition of Ca2+ accumulation by the drug is obtained with other local anaesthetics. The drug concentration required for 50% inhibition was 0.15 mM for dibucaine and 0.4 mM for both propranolol and tetracaine, whereas it was 5 mM, 8 mM and greater than 10 mM for lidocaine, benzocaine and procaine respectively. The heavy SR vesicles were only slightly affected by the incubation with propranolol or tetracaine in the presence of ATP, but their sensitivity increased markedly after storage at 0 degrees C for 24-48 h. These results suggest that propranolol and some local anaesthetics, in the presence of ATP, stimulate Ca2+ efflux by modifying a protein factor(s) rather than the phospholipid bilayer.


Sign in / Sign up

Export Citation Format

Share Document