The hypoglossal nucleus contains serotonin and several different serotonin receptors, and serotonin is present in fibers and terminals contacting hypoglossal motoneurons. Serotonin alters the excitability of hypoglossal motoneurons, and may influence hypoglossal motoneuron activity in a variety of physiological processes. Since the hypoglossal nucleus contains no serotoninergic somata, the present study sought to identify the sources of serotoninergic afferents to the hypoglossal nucleus. Fluorogold was injected into the hypoglossal nucleus and serotoninergic immunofluorescence was utilized in a dual-fluorescence technique to identify the sources of serotoninergic afferents to the hypoglossal nucleus. The results demonstrate that most serotoninergic afferents to the hypoglossal nucleus originate from the nuclei raphe pallidus and obscurus, while fewer originate from the nucleus raphe magnus and the parapyramidal region. Other regions of the medial tegmental field and the pons that contain both serotoninergic neurons and neuronal afferents to the hypoglossal nucleus contain no double-labeled neurons.

Retrospective administrative claims database studies provide real-world evidence about treatment patterns, healthcare resource use, and costs for patients and are increasingly used to inform policy-making, drug formulary, and regulatory decisions. However, there is no standard methodology to identify patients with pulmonary arterial hypertension (PAH) from administrative claims data. Given the number of approved drugs now available for patients with PAH, the cost of PAH treatments, and the significant healthcare resource use associated with the care of patients with PAH, there is a considerable need to develop an evidence-based and systematic approach to accurately identify these patients in claims databases. A panel of pulmonary hypertension clinical experts and researchers experienced in retrospective claims database studies convened to review relevant literature and recommend best practices for developing algorithms to identify patients with PAH in administrative claims databases specific to a particular research hypothesis.

Atrial natriuretic peptides (ANP) have recently been identified in both heart and CNS. These peptides possess potent natriuretic, diuretic, and vasorelaxant activities, and are all apparently derived from a single prohormone. Specific ANP binding sites have been characterized in the adrenal zona glomerulosa and kidney cortex, and one study reported ANP binding sites in the CNS. However, a detailed examination of the localization of ANP binding sites throughout the brain has not been reported. In this study, quantitative autoradiography was employed to examine the distribution of ANP receptors in the rat CNS. The binding of (3-125I-iodotyrosyl28) rat ANP-28 to binding sites in the rat CNS was saturable, specific for ANP-related peptides, and displayed high affinity (Kd = 600 pM). When the relative concentrations of ANP binding sites were determined throughout the rat brain, the highest levels of ANP binding were localized to the circumventricular organs, including the area postrema and subfornical organ, and the olfactory apparatus. Moderate levels of ANP binding sites were present throughout the midbrain and brain stem, while low levels were found in the forebrain, diencephalon, basal ganglia, cortex, and cerebellum. The presence of ANP binding sites in the subfornical organ and the area postrema, regions considered to be outside the blood-brain barrier, suggests that peripheral ANP levels may regulate some aspects of CNS control of salt and water balance. The possible functions of ANP binding sites in other regions of the rat brain are not known, but, like many other peptides, ANP may act as a neurotransmitter or neuromodulator at these loci.

We employed quantitative autoradiography to examine the distribution of thyrotropin-releasing hormone (TRH) receptors in the rat CNS. The binding of [3H]3-methyl-histidine-TRH [( 3H]MeTRH) to TRH receptors in frozen rat brain sections was saturable, of a high affinity (Kd = 5 nM), and specific for TRH analogs. Autoradiograms of [3H]MeTRH binding showed highest concentrations of TRH receptors in the rhinencephalon, including accessory olfactory bulb, nuclei of the amygdala, and the ventral dentate gyrus and subiculum of the hippocampus. Moderate TRH receptor concentrations were found within the thalamus and hypothalamus, in most regions of the rhombencephalon, such as the cranial nerve nuclei, and in the substantia gelatinosa of the spinal cord. Neocortex and basal ganglia contained low densities of TRH receptors. This distribution correlates well with the sensitivity of brain regions to the known effects of TRH, and suggests that TRH receptors may mediate the actions of TRH in the rat CNS.

Intracerebroventricular infusion of angiotensin II (Ang II) elicits a substantial sodium appetite in the rat. The present results demonstrate that this phenomenon consists of a small, early phase of sodium ingestion that is not the result of prior sodium loss but that thereafter urinary excretion of sodium exceeds intake and consequently the animals become hyponatremic and hypovolemic. The larger and more sustained bouts of sodium ingestion occurring 8-12 hr after the start of the Ang II infusion appear to represent a behavioral compensation for this incurred sodium deficit. These results confirm the arousal of a sodium appetite by action of Ang II on the brain but indicate the need for caution in assigning to it a direct and exclusive role in the neuroendocrine control of sodium intake.