Neuronal membrane sensitivity to a salmon calcitonin analogue with negligible ability to lower serum calcium.
The effects of [Gly8-des-Leu16-D-Arg24]-salmon calcitonin (CTA) on spontaneous extracellular activity and the passive membrane properties of rat forebrain neurons were studied in vivo and in vitro. This analogue had negligible ability to lower serum calcium relative to salmon calcitonin (SCT), however, the pattern of neuronal membrane sensitivity to CTA was similar to that produced by SCT and calcitonin generelated peptide. Depression of extracellularly recorded spontaneous action potential firing rate was the predominant response of neurons to microiontophoretic application of each peptide in vivo. Intracellular recordings from septal neurons suggest that the extracellularly observed inhibitory effects may be due to changes in membrane potential. We conclude that different structure-activity relationships may apply to the pharmacological effects of calcitonin in brain and its serum calcium-lowering action.
Twery
M J
MJ
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77550.
Joëls
M
M
Gallagher
J P
JP
Orlowski
R C
RC
Moss
R L
RL
D000200:Action Potentials / Q000187:drug effects; D000679:Amygdala / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000502:physiology; D002116:Calcitonin / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide; D002118:Calcium / Q000097:blood*; D005625:Frontal Lobe / Q000187:drug effects / Q000502:physiology*; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009479:Neuropeptides / Q000494:pharmacology; D051381:Rats; D013788:Thalamus / Q000187:drug effects / Q000502:physiology
D009479:Neuropeptides; C028815:salmon calcitonin; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide; D002118:Calcium