galantide and galanin-(1-13)-spantide-amide

The Brattleboro rat eats spontaneously 46% of its diet per day in fat when given a choice of carbohydrate, protein and fat. An overexpression of galanin (GAL) has been also observed in the hypothalamic paraventricular nuclei (PVN). This associative correlation has led to a hypothesis of a functional relation between central galanin expression and the preference for a lipid diet. In the present experiments, the effects of two GAL receptor antagonists, C7 and galantide, on fat consumption and central overexpression of GAL were investigated. Both antagonists were injected into either the cerebral ventricles or directly above the PVN, and the diet consumption followed for the subsequent 24h. C7 decreased significantly fat consumption when injected into the ventricles or directly above the PVN. In contrast, galantide must be injected above the PVN to show the same effect. However, the two antagonists did not modify GAL mRNA expression in the PVN when they were injected 2h before sacrifice. These experiments confirm a functional link between the preferential consumption of fat and hypothalamic Galanin; different subtypes of the GAL receptor are probably involved, since both Galanin antagonists were differently efficient in decreasing spontaneous fat selection of the Brattleboro rat.

Topics: Animals; Dietary Fats; Food Preferences; Galanin; Hypothalamus; In Situ Hybridization; Injections, Intraventricular; Male; Peptide Fragments; Rats; Rats, Brattleboro; Receptors, Galanin; Receptors, Neuropeptide; RNA, Messenger; Substance P

Galanin is a neuropeptide that causes a marked pressor response in several non-mammalian vertebrate species, and some marsupials. In this study, the effect of three galanin antagonists were tested on the pressor response to an intravenous dose (6.3 nmol/kg) of porcine galanin in anaesthetised Cane toads, Bufo marinus. Antagonists were injected at either 20 or 50 times the molar dose (x MD) of galanin. The antagonist, C7 (Galanin 1-13-spantide) reduced the pressor effect of galanin by 32.2 +/- 6.0% when delivered at 20 x MD (n = 4) and by 42.9 +/- 15.7% when delivered at 50 x MD (n = 4) of galanin, the response recovering within 30 min. A second antagonist, M32a (Galanin 1-13-NPY 24-36) had no effect on the pressor response to galanin at 20 x MD (n = 4), but significantly reduced the pressor effect by 54.8 +/- 6.4% at 50 x MD (n = 5), which also recovered within 30 min. Administration of a third antagonist, galantide or M15 (Galanin 1-13-Substance P5-11), resulted in a profound drop in blood pressure, and did not affect the response to galanin at either dose. In conclusion, C7 and M32a are effective, short-term antagonists of the blood pressure effects of galanin in the toad.

Topics: Animals; Blood Pressure; Bufo marinus; Galanin; Heart Rate; Neuropeptide Y; Peptide Fragments; Recombinant Fusion Proteins; Substance P; Swine; Vasoconstrictor Agents

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.

Topics: Analysis of Variance; Animals; Aortic Bodies; Blood Pressure; Cats; Electric Stimulation; Female; Galanin; Heart; Heart Conduction System; Male; Neuropeptides; Peptide Fragments; Peptides; Substance P; Sympathetic Nervous System; Vagus Nerve