Expression and localisation of somatostatin receptor subtypes sst1–sst5 in areas of the rat medulla oblongata involved in autonomic regulation

Spary, Emma J.; Maqbool, Azhar; Batten, Trevor

doi:10.1016/j.jchemneu.2007.06.002

Cited by 28 publications

(41 citation statements)

References 77 publications

(90 reference statements)

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“…This pattern of expression is consistent with previous investigations at other sites 20 -23 and extends recent work by Spary et al, 11 which colocalized sst2A with phenylethanolamine N-methyltransferase (PNMT) containing neurons in more caudal, ventral medulla. We used wellcharacterized sstR antibodies 23 of which the specificity has been validated by controls, including incubation of primary antibodies together with immunizing peptide 11,24 and adsorption controls for Western and immunoblotting. 23,25 Other control experiments included tissue incubation without primary antibodies 11 (present study).…”

Section: Discussionsupporting

confidence: 92%

“…Approximately half of the bulbospinal catecholamine containing VGlut2-positive neurons and one third of bulbospinal enkephalinergic neurons but not adjacent GABAergic neurons contained sst2A, consistent with a sympathetic premotor function. 11,26 The sst2A receptor was present on the soma and dendrites of bulbospinal neurons but not on terminal boutons within the RVLM, indicating that into the RVLM of urethane-anesthetized and vagotomized rats substantially reduced HR, MAP, and sSNA but had little effect on PNA (A). After 2 hours of recovery, the spinal cord was transected (Spx) and the animal euthanized (KCl; A).…”

Section: Discussionmentioning

confidence: 99%

“…We used wellcharacterized sstR antibodies 23 of which the specificity has been validated by controls, including incubation of primary antibodies together with immunizing peptide 11,24 and adsorption controls for Western and immunoblotting. 23,25 Other control experiments included tissue incubation without primary antibodies 11 (present study). The sensitivity of the antibodies was appropriate, because distinct labeling for sst1 and sst2B was evident in the spinal cord, as reported previously, 20 and for sst4 within the nucleus ambiguus, despite little or no labeling within the RVLM.…”

Section: Discussionmentioning

confidence: 99%

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Somatostatin 2A Receptor-Expressing Presympathetic Neurons in the Rostral Ventrolateral Medulla Maintain Blood Pressure

Burke

Costin

et al. 2008

Hypertension

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Abstract-Bulbospinal neurons in the rostral ventrolateral medulla (RVLM) are critical for the maintenance of sympathetic vasomotor tone and normal cardiovascular reflex function. So far, selectively eliminating/inhibiting distinct subpopulations of RVLM neurons has not significantly altered arterial pressure. Here we show that RVLM presympathetic neurons that express somatostatin 2A receptors are essential for maintaining and potentially generating sympathetic vasomotor tone. Combined immunocytochemistry and in situ hybridization were used to map the expression of somatostatin receptors 1, 2A, 2B, 3, and 4 (sst1 through 4, respectively) in the rat RVLM. sst1 and sst2B were absent; sst3 and sst4 were sparse. However, sst2A was found postsynaptically and detected in 35Ϯ5% of bulbospinal RVLM neurons a population that included 54Ϯ4% of catecholaminergic and 30Ϯ3% of enkephalinergic neurons. Bilateral microinjection into the RVLM of either somatostatin or the receptor-selective agonist lanreotide evoked dramatic, dose-dependent sympathoinhibition, hypotension, and bradycardia that were blocked by the sst2 receptor antagonist BIM-23627 in anesthetized rats. Bilateral RVLM microinjection of somatostatin also attenuated chemoreceptor and somatosympathetic reflex function. Somatostatin only eliminated the first sympathoexcitatory peak evoked by somatosympathetic reflex activation, whereas muscimol abolished both excitatory peaks providing functional evidence that the activity of only a subpopulation of RVLM presympathetic neurons is inhibited by somatostatin. We suggest that the subpopulation of bulbospinal RVLM neurons that expresses the sst2A receptor sets sympathetic vasomotor output. These neurons are essential for maintaining resting blood pressure under anesthesia and contribute to adaptive reflexes mediated through the RVLM. Key Words: cardiovascular Ⅲ sympathetic vasomotor tone Ⅲ catecholamine Ⅲ enkephalin Ⅲ respiration P resympathetic neurons within the rostral ventrolateral medulla (RVLM) contain catecholamines and/or preproenkephalin (PPE) and are critical for the tonic and reflex control of arterial pressure (AP). [1][2][3] Inputs regulating RVLM presympathetic neuronal activity release amino acids and/or a range of modulatory neurochemicals, including peptides. [2][3][4][5][6] These underlie the ability to provide a differentiated sympathetic drive to the various vascular beds, 6 alter the responses to reflex activation, 5 and set the level of AP. 1,3,5 Identification of neurons responsible for generating and maintaining sympathetic vasomotor tone and, therefore, setting the level of AP would be a major breakthrough in understanding circulatory control.The inhibitory neuropeptide somatostatin (SST) is distributed widely in regions of the central nervous system involved in motor, cognitive, autonomic, and neuroendocrine processes. 7,8 Two biologically active forms of SST, SST 14 and SST 28, are cleaved from preprosomatostatin and bind to all of the SST receptors with similar affinity. 8 Six G protein-couple...

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Somatostatin 2A Receptor-Expressing Presympathetic Neurons in the Rostral Ventrolateral Medulla Maintain Blood Pressure

Burke

Costin

et al. 2008

Hypertension

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“…In line with the mapping of the ligand, the sst receptors are widely expressed in the rodent brain with the following regional pattern: all layers of the cerebral cortex (sst 1 , sst 2a/b , sst 3 , sst 4 ), bed nucleus of the stria terminalis (sst 1 , sst 2a, b , sst 4 ), hippocampus (sst 1 , sst 2a, b , sst 3 , sst 4 ), basolateral amygdaloid nucleus (sst 1 , sst 2a/b , sst 3 , sst 4 ), medial amygdaloid nucleus (sst 1 , sst 2 , sst 3 ), ventromedial hypothalamic nucleus (sst 1 , sst 2 , sst 3 ), dorsomedial hypothalamic nucleus (sst 1 , sst 3 ), paraventricular nucleus (sst 2a , sst 3 ) and arcuate nucleus of the hypothalamus (sst 1 , sst 2a , sst 3 , sst 4 ), substantia nigra (sst 1 , sst 2a/b , sst 3 ), dorsal raphe nucleus (sst 1 , sst 2 , sst 3 ), locus coeruleus (sst 2 , sst 3 ), granular layer of the cerebellum (sst 1 , sst 2b , sst 3 , sst 4 , sst 5 ), dorsal motor nucleus of the vagus nerve (sst 2a, b , sst 4 , sst 5 ) and nucleus of the solitary tract (sst 1 , sst 2 , sst 3 ) (Schindler and Humphrey, 1999; Fehlmann et al, 2000; Schulz et al, 2000; Hannon et al, 2002b; Videau et al, 2003; Spary et al, 2008; Kumar, 2012). With regards to the truncated sst 5 variants, they show a distinct distribution with a high abundance of full length sst 5 in mouse hypothalamus and cerebellum followed by sst 5 TMD2 and sst 5 TMD1, whereas sst 5 TMD4 is not detectable (Hannon et al, 2002b; Cordoba-Chacon et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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

Stengel

Taché

2017

Front. Neurosci.

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Corticotropin-releasing factor (CRF) is the hallmark brain peptide triggering the response to stress and mediates—in addition to the stimulation of the hypothalamus-pituitary-adrenal (HPA) axis—other hormonal, behavioral, autonomic and visceral components. Earlier reports indicate that somatostatin-28 injected intracerebroventricularly counteracts the acute stress-induced ACTH and catecholamine release. Mounting evidence now supports that activation of brain somatostatin signaling exerts a broader anti-stress effect by blunting the endocrine, autonomic, behavioral (with a focus on food intake) and visceral gastrointestinal motor responses through the involvement of distinct somatostatin receptor subtypes.

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“…With regards to feeding regulatory centers, a dense expression of sst receptors has been detected in the dorsomedial hypothalamic nucleus (sst 1 = sst 3 ), ventromedial hypothalamic nucleus (sst 1 > sst 3 > sst 2 ), PVN (sst 2a = sst 3 ) and Arc of the hypothalamus (sst 1 = sst 2a = sst 3 > sst 4 ), the NTS (sst 1 = sst 2 > sst 3 ) and the dorsal motor nucleus of the vagus nerve (sst 2a/b = sst 4 > sst 5 ) (Fehlmann et al, 2000; Hannon et al, 2002; Schindler et al, 1999; Schulz et al, 2000; Spary et al, 2008). Therefore, in feeding regulatory nuclei such as the Arc, PVN and NTS, both ligands and receptors are expressed.…”

Section: Brain Somatostatin Signaling and The Regulation Of Feeding Bmentioning

confidence: 99%

The role of brain somatostatin receptor 2 in the regulation of feeding and drinking behavior

Stengel

Karasawa

Taché

2015

Hormones and Behavior

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Somatostatin was discovered four decades ago as hypothalamic factor inhibiting growth hormone release. Subsequently, somatostatin was found to be widely distributed throughout the brain and to exert pleiotropic actions via interaction with five somatostatin receptors (sst1-5) that are also widely expressed throughout the brain. Interestingly, in contrast to the predominantly inhibitory actions of peripheral somatostatin, the activation of brain sst2 signaling by intracerebroventricular injection of stable somatostatin agonists potently stimulates food intake and independently, drinking behavior in rodents. The orexigenic response involves downstream orexin-1, neuropeptide Y1 and μ receptor signaling while the dipsogenic effect is mediated through the activation of the brain angiotensin 1 receptor. Brain sst2 activation is part of mechanisms underlying the stimulation of feeding and more prominently water intake in the dark phase and is able to counteract the anorexic response to visceral stressors.

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Expression and localisation of somatostatin receptor subtypes sst1–sst5 in areas of the rat medulla oblongata involved in autonomic regulation

Cited by 28 publications

References 77 publications

Somatostatin 2A Receptor-Expressing Presympathetic Neurons in the Rostral Ventrolateral Medulla Maintain Blood Pressure

Somatostatin 2A Receptor-Expressing Presympathetic Neurons in the Rostral Ventrolateral Medulla Maintain Blood Pressure

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

The role of brain somatostatin receptor 2 in the regulation of feeding and drinking behavior

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