Enzymatic degradation of somatostatin by rat plasma and hypothalamus

1978 ◽  
Vol 56 (5) ◽  
pp. 840-843 ◽  
Author(s):  
A. Dupont ◽  
G. Alvarado-Urbina ◽  
J. Côté ◽  
F. Labrie

A highly sensitive and specific radioimmunoassay for somatostatin has been used to study inactivation of the neurohormone by plasma and hypothalamic peptidase(s). Specificity of the inactivation process was indicated by the absence of interference by addition of luteinizing hormone releasing hormone, thyrotropin-releasing hormone, oxytocin, or substance P. The inactivating ability of hypothalamic tissue and plasma was destroyed by heating and the protease inhibitor benzamidine prevented plasma activity, thus suggesting the enzymatic nature of the processes involved. The present data suggest that the inactivation of somatostatin by hypothalamus and plasma could be an important factor in the regulation of circulating somatostatin levels.

1982 ◽  
Vol 37 (8) ◽  
pp. 1075-1081 ◽  
Author(s):  
Karl Folkers ◽  
Cyril Y. Bowers ◽  
Wilson B. Lutz ◽  
Klaus Friebel ◽  
Teresa Kubiak ◽  
...  

Abstract Seven new analogs of the luteinizing hormone releasing hormone (LHRH), having an Azagly10 moiety, and three corresponding Gly10 -analogs were synthesized for bioassay and comparison of inhibitory potencies. This study was toward a possible advantage of the Azagly10 moiety to minimize C-terminal degradation, in vivo. Of the three procedures which were studied to achieve Azagly10-peptides, the reaction of cyanate ion with hydrazides was the most favorable. Variations of substitution in position 1 were also studied. The data from the antiovulatory assay showed that an Azagly10 moiety may not depress activity, and may allow equal or even higher activity than the Gly10 moiety, depending on the analog. [N-Ac-D-Thr1 , D-p-Cl-Phe2 , D-Trp3,6, Azagly10]-LHRH was more inhibitory than the corresponding Gly10-analog. Based on pairs of analogs, the following relationships appeared: (1) N-Ac-D-Thr1 was more effective than N-Ac-p-Cl-Phe1 ; (2) The L-configuration of Ala as N-Ac-Ala1- was more effective than the D-; (3) N-Ac-Ala1 appeared more effective than the N-Ac-D-Thr1 ; (4) D-Trp6 appeared more effective than D-Phe6. In an ultimate clinical use of an antagonist of LHRH to block ovulation, the Azagly10 moiety may be advantageous for limitation of enzymatic degradation.


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