title: Somatostatin in the rat rostral ventrolateral medulla: Origins and mechanism of action.
abstract: Somatostatin (SST) or agonists of the SST-2 receptor (sst2 ) in the rostral ventrolateral medulla (RVLM) lower sympathetic nerve activity, arterial pressure, and heart rate, or when administered within the Bötzinger region, evoke apneusis. Our aims were to describe the mechanisms responsible for the sympathoinhibitory effects of SST on bulbospinal neurons and to identify likely sources of RVLM SST release. Patch clamp recordings were made from bulbospinal RVLM neurons (n = 31) in brainstem slices prepared from juvenile rat pups. Overall, 58% of neurons responded to SST, displaying an increase in conductance that reversed at -93 mV, indicative of an inwardly rectifying potassium channel (GIRK) mechanism. Blockade of sst2 abolished this effect, but application of tetrodotoxin did not, indicating that the SST effect is independent of presynaptic activity. Fourteen bulbospinal RVLM neurons were recovered for immunohistochemistry; nine were SST-insensitive and did not express sst2a . Three out of five responsive neurons were sst2a -immunoreactive. Neurons that contained preprosomatostatin mRNA and cholera-toxin-B retrogradely transported from the RVLM were detected in: paratrigeminal nucleus, lateral parabrachial nucleus, Kölliker-Fuse nucleus, ventrolateral periaqueductal gray area, central nucleus of the amygdala, sublenticular extended amygdala, interstitial nucleus of the posterior limb of the anterior commissure nucleus, and bed nucleus of the stria terminalis. Thus, those brain regions are putative sources of endogenous SST release that, when activated, may evoke sympathoinhibitory effects via interactions with subsets of sympathetic premotor neurons that express sst2 .
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, 2109, NSW, Australia.
authors.forename: Lama
authors.initials: L
authors.lastname: Bou Farah
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, 2109, NSW, Australia.
authors.forename: Belinda R
authors.initials: BR
authors.lastname: Bowman
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, 2109, NSW, Australia.
authors.forename: Phil
authors.initials: P
authors.lastname: Bokiniec
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, 2109, NSW, Australia.
authors.forename: Shafinaz
authors.initials: S
authors.lastname: Karim
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, 2109, NSW, Australia.
authors.forename: Sheng
authors.initials: S
authors.lastname: Le
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, 2109, NSW, Australia.
authors.forename: Ann K
authors.initials: AK
authors.lastname: Goodchild
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, 2109, NSW, Australia.
authors.forename: Simon
authors.initials: S
authors.lastname: McMullan
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002772:Cholera Toxin / Q000378:metabolism; D057809:HEK293 Cells; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008526:Medulla Oblongata / Q000166:cytology* / Q000254:growth & development; D008845:Microinjections; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D018408:Patch-Clamp Techniques; D010487:Periaqueductal Gray / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism* / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D006728:Hormones; D018040:Receptors, Neurokinin-1; D017481:Receptors, Somatostatin; C106140:somatostatin receptor sst2A; D013004:Somatostatin; D002772:Cholera Toxin; D014446:Tyrosine 3-Monooxygenase; C013411:biocytin; D008239:Lysine
keywords: GIRK; RVLM; patch clamp; retrograde tracing; somatostatin; sst2a