Functional effects of a family of galanin antagonists on the cardiovascular system in anaesthetised cats.
Previous studies have shown that injection of galanin (GAL: 6.2 nmol/kg) causes prolonged inhibition of cardiac vagal action in anaesthetised cats. Stimulation of the cardiac sympathetic nerve (16 Hz for 5 min) also produces inhibition of cardiac vagal action, an effect which has been proposed to be due to the release of endogenous GAL from sympathetic nerves. In a previous study we tested galantide (M15) and in this study we compared galantide with two other GAL antagonists for their GAL antagonist activity in our experimental model. Each of these incorporate the N-terminal fragment GAL 1-13 and a C-terminal portion of another bioactive peptide and all are C-terminally amidated. GAL 1-13 Substance P 5-11 amide (galantide: M15: 62 nmol/kg and 156 nmol/kg), GAL 1-13 Spantide amide (C7: 156 nmol/kg) and GAL 1-13 NPY 24-36 amide (M32a: 62 nmol/kg) all significantly reduced the cardiac vagal inhibitory effect of exogenous GAL and also reduced the effect of sympathetic stimulation on subsequent cardiac vagal slowing, giving strong support to our hypothesis that GAL is involved in this phenomenon. No antagonist reduced the depressor effect of GAL. This study demonstrates the GAL antagonist properties of these agents on autonomic neuroeffector functions making them useful tools in elucidating further functions of endogenous GAL.
Ulman
L G
LG
Prince of Wales Medical Research Institute, Prince of Wales Hospital, Randwick, Sydney, Australia.
Potter
E K
EK
McCloskey
D I
DI
D000704:Analysis of Variance; D000818:Animals; D001016:Aortic Bodies / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D004558:Electric Stimulation; D005260:Female; D019004:Galanin / Q000031:analogs & derivatives; D006321:Heart / Q000294:innervation; D006329:Heart Conduction System / Q000187:drug effects*; D008297:Male; D009479:Neuropeptides / Q000037:antagonists & inhibitors*; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000502:physiology; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
D009479:Neuropeptides; D010446:Peptide Fragments; D010455:Peptides; C074975:galantide; C079788:galanin (1-13)-spantide amide; D013373:Substance P; D019004:Galanin