Analogue separates biological effects of salmon calcitonin on brain and renal cortical membranes.
The conformation-activity relationship of salmon calcitonin in kidney and brain was investigated with regard to effects on membrane binding and adenylate cyclase activity. Since an amphipathic alpha-helical conformation on the calcitonin molecule is associated with high potency in lowering serum calcium, the activity of the parent peptide was compared to that of [Gly8, D-Arg24]des-Leu16-salmon calcitonin, a calcitonin analogue (CTA) with less helix forming potential. The results indicate that while salmon calcitonin possesses similar potency in brain and kidney, CTA is effective only in brain. Furthermore, CTA did not inhibit the binding of 125I-labeled human calcitonin gene-related peptide (HCGRP) to brain membranes. Our findings suggest that the specific binding and effects of salmon calcitonin on adenylate cyclase activity in brain do not depend on conformational features in the middle region of the molecule, although the alpha-helical structure in this region does appear to be an important property for salmon calcitonin binding to renal cortical membranes.
Twery
M J
MJ
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77550.
Seitz
P K
PK
Nickols
G A
GA
Cooper
C W
CW
Gallagher
J P
JP
Orlowski
R C
RC
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002116:Calcitonin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology; D009928:Organ Specificity; D011487:Protein Conformation; D051381:Rats; D013329:Structure-Activity Relationship
D009479:Neuropeptides; C058809:calcitonin, salmon, Gly(8)-des-Leu(16)-Arg(24)-; C028815:salmon calcitonin; D002116:Calcitonin; D000262:Adenylyl Cyclases; D015740:Calcitonin Gene-Related Peptide