Interaction of adrenomedullin with calcitonin receptor in cultured human breast cancer cells, T 47D.
Human adrenomedullin (hADM), human calcitonin gene-related peptide (hCGRP), and salmon calcitonin (sCT)-activated adenylyl cyclase with EC50 values of 132, 764, and 0.5 nM, respectively, in human breast cancer cell line, T 47D. Treatment of T 47D cell membranes with near maximal concentrations of sCT, hADM and hCGRP had no additive effect on adenylyl cyclase activity. Salmon calcitonin (8-32)[sCT (8-32)], selective antagonist of calcitonin receptor, inhibited the activation of adenylyl cyclase by these three peptides. On the other hand, the putative ADM receptor antagonist, ADM (22-52), and CGRP receptor antagonist, CGRP (8-37), failed to inhibit ADM-, CGRP- or sCT-activated adenylyl cyclase. These results suggest that in T47D cells, both ADM and CGRP activated adenylyl cyclase through sCT receptors.
Disa
J
J
Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA.
Dang
K
K
Tan
K B
KB
Aiyar
N
N
D000262:Adenylyl Cyclases / Q000378:metabolism; D053607:Adrenomedullin; D001943:Breast Neoplasms / Q000378:metabolism; D002116:Calcitonin / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D058265:Receptors, Adrenomedullin; D018003:Receptors, Calcitonin / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D018000:Receptors, Peptide; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D008565:Membrane Proteins; D010446:Peptide Fragments; D010455:Peptides; D058265:Receptors, Adrenomedullin; D018003:Receptors, Calcitonin; D018000:Receptors, Peptide; C104782:adrenomedullin (22-52); C058636:calcitonin gene-related peptide (8-37); D053607:Adrenomedullin; C028815:salmon calcitonin; D002116:Calcitonin; D000262:Adenylyl Cyclases; D015740:Calcitonin Gene-Related Peptide