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 .

Neural activity in the periaqueductal gray and other specific subcortical structures is enhanced when a selective serotonin reuptake inhibitor selectively prevents seizure‐induced sudden death in the DBA/1 mouse model of sudden unexpected death in epilepsy

“…38 The enhancement of PAG activity is also consistent with the critical roles this structure normally plays to compensate for respiratory distress caused by numerous physiological challenges and also in enhancing arousal. 22,46,49,50 The pontine raphe nucleus was the only raphe nucleus that showed significantly increased activity when fluoxetine selectively blocked S-IRA, but the basis for this selective effect is unclear and needs to be investigated further. This is consistent with recent evidence indicating that this compensatory role of the PAG may be deficient in DBA/1 mice.…”

“…49 This pattern of activation is proposed to be critical to the ability of fluoxetine to prevent the seizure from inducing terminal apnea, as such increase was not seen with fluoxetine when seizure was not evoked. Other respiratory structures, including the nucleus of the solitary tract, parabrachial, and hypoglossal nucleus, may also become involved.…”

Activation of Brain Somatostatin Signaling Suppresses CRF Receptor-Mediated Stress Response

“…Its actions include increased locomotor activity (Viollet et al, 2008), memory and learning (Vecsei and Widerlov, 1988; Gastambide et al, 2009), and sleep (Steiger, 2007; Xu et al, 2015), as well as changes in autonomic cardiovascular and gastric functions (e.g., sympatho-inhibitory effect with lowering of heart rate and blood pressure, stimulation of gastric secretion and transit) (Brown and Taché, 1981; Martinez et al, 2000; Bou Farah et al, 2016), immune functions (Gonzalez-Rey et al, 2015) and ingestive behaviors (e.g., increased feeding and drinking; Stengel et al, 2015). Of importance in relation with stress, injection of somatostatin into the brain influences emotional processes exerting anxiolytic and anti-depressant effects (Engin and Treit, 2009; Scheich et al, 2016).…”

Somatostatin 2a receptors are not expressed on functionally identified respiratory neurons in the ventral respiratory column of the rat

“…Both antibodies have been extensively characterized by western and dotblot assay; neither label sst 2 knockout animals, and the rabbit antibody selectively labels HEK cells transfected with sst 2 (Schulz et al, ; Korner et al, ; Fischer et al, ). As recently described, binding of both antisera is blocked by preabsorption with the sst 2a antigen, and overlaps completely in tissue incubated with both primary antibodies, visualized with different fluorescent secondary antibodies (Bou Farah et al, ).…”