Galanin antagonist effects on cardiac vagal inhibitory actions of sympathetic stimulation in anaesthetized cats and dogs.

Ulman, Lesley G.; Moriarty, Mark; Potter, Erica K.; McCloskey, D.I.

doi:10.1113/jphysiol.1993.sp019647

Cited by 26 publications

(9 citation statements)

References 15 publications

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“…Exogenous galanin may reduce the heart rate response to peripheral stimulation of the right vagus nerve in the mouse [4,18] and cat [41] in-vivo, but this was not observed in the rat [42] or dog [43]. Systemic infusion of neuropeptides in-vivo is also complicated by potential changes in haemodynamics and other circulating factors complicating the interpretation of data.…”

Section: Discussionmentioning

confidence: 99%

The cardiac sympathetic co-transmitter galanin reduces acetylcholine release and vagal bradycardia: Implications for neural control of cardiac excitability

Herring

Cranley

Lokale

et al. 2012

Journal of Molecular and Cellular Cardiology

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The autonomic phenotype of congestive cardiac failure is characterised by high sympathetic drive and impaired vagal tone, which are independent predictors of mortality. We hypothesize that impaired bradycardia to peripheral vagal stimulation following high-level sympathetic drive is due to sympatho-vagal crosstalk by the adrenergic co-transmitters galanin and neuropeptide-Y (NPY). Moreover we hypothesize that galanin acts similarly to NPY by reducing vagal acetylcholine release via a receptor mediated, protein kinase-dependent pathway. Prolonged right stellate ganglion stimulation (10 Hz, 2 min, in the presence of 10 μM metoprolol) in an isolated guinea pig atrial preparation with dual autonomic innervation leads to a significant (p < 0.05) reduction in the magnitude of vagal bradycardia (5 Hz) maintained over the subsequent 20 min (n = 6). Immunohistochemistry demonstrated the presence of galanin in a small number of tyrosine hydroxylase positive neurons from freshly dissected stellate ganglion tissue sections. Following 3 days of tissue culture however, most stellate neurons expressed galanin. Stellate stimulation caused the release of low levels of galanin and significantly higher levels of NPY into the surrounding perfusate (n = 6, using ELISA). The reduction in vagal bradycardia post sympathetic stimulation was partially reversed by the galanin receptor antagonist M40 after 10 min (1 μM, n = 5), and completely reversed with the NPY Y2 receptor antagonist BIIE 0246 at all time points (1 μM, n = 6). Exogenous galanin (n = 6, 50–500 nM) also reduced the heart rate response to vagal stimulation but had no effect on the response to carbamylcholine that produced similar degrees of bradycardia (n = 6). Galanin (500 nM) also significantly attenuated the release of 3H-acetylcholine from isolated atria during field stimulation (5 Hz, n = 5). The effect of galanin on vagal bradycardia could be abolished by the galanin receptor antagonist M40 (n = 5). Importantly the GalR1 receptor was immunofluorescently co-localised with choline acetyl-transferase containing neurons at the sinoatrial node. The protein kinase C inhibitor calphostin (100 nM, n = 6) abolished the effect of galanin on vagal bradycardia whilst the protein kinase A inhibitor H89 (500 nM, n = 6) had no effect. These results demonstrate that prolonged sympathetic activation releases the slowly diffusing adrenergic co-transmitter galanin in addition to NPY, and that this contributes to the attenuation in vagal bradycardia via a reduction in acetylcholine release. This effect is mediated by GalR1 receptors on vagal neurons coupled to protein kinase C dependent signalling pathways. The role of galanin may become more important following an acute injury response where galanin expression is increased.

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Section: Discussionmentioning

confidence: 99%

The cardiac sympathetic co-transmitter galanin reduces acetylcholine release and vagal bradycardia: Implications for neural control of cardiac excitability

Herring

Cranley

Lokale

et al. 2012

Journal of Molecular and Cellular Cardiology

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“…1985). A recently developed galanin antagonist, galantide, blocks the inhibitory action of galanin on the cat cardiac vagus, but does not attenuate the depressor action of galanin in the same animals (Ulman et al 1993b). Thus, it is likely that the inhibitory effect of galanin on vascular smooth muscle is mediated by a receptor type distinct from that located on the vagus nerve.…”

Section: Galaninmentioning

confidence: 99%

Peptides as Neurotransmitters in Vascular Autonomic Neurons

Morris

1995

Clin Exp Pharma Physio

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1. Neuropeptides are present in the majority of autonomic neurons projecting to blood vessels, where they are co-localized with non-peptide transmitters and sometimes with other peptides. 2. Neuropeptides are released from vasoconstrictor and vasodilator nerve terminals after high frequency stimulation ( > 2-5Hz) with trains of impulses. 3. Neuropeptides can have potent post-synaptic effects on vascular tone, but often these effects are restricted to selected regions of the vasculature. 4. Post-synaptic effects of neuropeptides tend to be more slowly-developing and more long-lasting than those of non-peptide transmitters. 5. Autonomic vasoconstrictor and vasodilator responses often have multiple phases, with the faster phases being mediated by non-peptide transmitters and the slower phases medicated predominantly by one or more neuropeptides. 6. Some neuropeptides do not seem to have post-synaptic effects in a particular vascular bed, but can have presynaptic actions on neurotransmitter release. 7. Neuropeptides form an important component of the repertoire of neurotransmitters used by vascular autonomic neurons to regulate regional blood flow in response to a range of physiological stimuli.

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“…Additional galanin receptor subtypes are also suggested from studies with chimeric peptides (e.g. M15, M35 and M40), which act as antagonists in functional assays in the cardiovascular system (Ulman et al ., 1993), spinal cord (Wiesenfeld‐Hallin et al ., 1992), locus coeruleus, hippocampus (Bartfai et al ., 1991) and hypothalamus (Leibowitz and Kim, 1992; Bartfai et al ., 1993), but exhibit agonist activity at some peripheral sites (Bartfai et al ., 1993; Gu et al ., 1995). The chimeric peptides M15, M32, M35, M40 and C7 are agonists at GAL 1 receptors expressed endogenously in Bowes human melanoma cells (Ohtaki et al ., 1999), and at heterologously expressed recombinant GAL 1 , GAL 2 and GAL 3 receptors (Smith et al ., 1997; Fitzgerald et al ., 1998; Smith et al ., 1998).…”

Section: Galaninmentioning

confidence: 99%