Biomedical subjects

H E Reed

Publications and source records attributed to H E Reed.

5 recordsLinked to original sources

PubMed2002

Effects of vasoactive intestinal polypeptide on neurones of the rat suprachiasmatic nuclei in vitro.

The suprachiasmatic nuclei (SCN) of the hypothalamus house the main circadian pacemaker in mammals. Vasoactive intestinal polypeptide (VIP) is the most abundant neuropeptide in the SCN and has been shown to phase-shift the electrical activity rhythm of SCN cells in vitro. However, the effects of VIP on the cellular activity of rat SCN neurones are unknown. In this study, we examined the acute effects of VIP on the extracellularly recorded spontaneous firing rate of SCN neurones in an in-vitro hypothalamic slice preparation. Furthermore, with the use of receptor-selective agonists and antagonists, we determined which receptors might mediate the effects of VIP in the SCN. Approximately 50% of cells responded to VIP; the main type of response was suppression in firing rate, although a few cells were activated. Suppression responses to VIP were mimicked by the VPAC(2) receptor agonist Ro 25-1553 and blocked by the selective VPAC(2) receptor antagonist PG 99-465. The PAC(1) receptor agonist maxadilan evoked responses from 40% of SCN cells, and activations to this agonist were not altered by PG 99-465. Responses to VIP were not blocked by antagonists to ionotropic glutamate receptors, but the duration of suppression was modulated by the GABA(A) receptor antagonist bicuculline. Our data indicate that VIP alters the electrical activity of rat SCN neurones in vitro, via both VPAC(2) and PAC(1) receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2001

Vasoactive intestinal polypeptide (VIP) phase-shifts the rat suprachiasmatic nucleus clock in vitro.

In mammals, the principal circadian pacemaker is housed in the hypothalamic suprachiasmatic nuclei (SCN). The SCN exhibit high levels of vasoactive intestinal polypeptide (VIP) immunoreactivity and two of the three VIP receptors, VPAC(2) and PAC(1), are found in the rat SCN. However, the role of VIP in the SCN remains unclear. In this study, we examined the phase-resetting actions of VIP and selective VIP receptor agonists on the electrical activity rhythm of rat SCN neurons in vitro. Application of VIP during the subjective day did not shift the peak in the firing rate rhythm. However, VIP treatment during the early or late subjective night evoked a small phase delay or a large phase advance, respectively. The phase-advancing effect of VIP was reproduced by the novel VPAC(2) receptor agonist RO 25-1553, but not by pituitary adenylate cyclase-activating peptide (a potent PAC(1) receptor agonist), or by [K15,R16,L27]VIP(1-7)/GRF(8-27), a novel, selective VPAC(1) receptor agonist. These data show that VIP phase-dependently phase-resets the rodent SCN pacemaker in vitro, presumably via the VPAC(2) receptor. As the pattern of phase-shifting evoked by VIP and RO 25-1553 resembles the phase-resetting actions of light on rodent behavioural rhythms, these data support a role for VIP and the VPAC(2) receptor in photic entrainment of the rodent circadian pacemaker.

Action Potentials↗

PubMed1996

Amplification of the thapsigargin-evoked increase in the cytosolic free Ca2+ concentration by acetylcholine in acutely isolated mouse submandibular acinar cells.

The intracellular Ca2+ concentration was measured in single, acutely isolated, mouse submandibular acinar cells loaded with fura-2 AM. All experiments were performed in the absence of extracellular Ca2+ in order to eliminate Ca2+ influx. The microsomal ATPase inhibitor, thapsigargin, was used to release Ca2+ from intracellular stores and simultaneously prevent re-uptake into the stores. Sequential application of thapsigargin (2 microM) and the Ca2+ ionophore ionomycin (500 nM) indicated that thapsigargin was able to mobilize practically all intracellular Ca2+. Furthermore, in comparison with results obtained following inhibition of the plasma membrane Ca(2+)-ATPase by La3+ (2 mM), it may be shown that slowly unloading the intracellular Ca2+ stores using thapsigargin does not normally cause a massive, cytotoxic, increase in the cytosolic Ca2+ concentration, because Ca2+ is rapidly extruded from the cell across the plasma membrane. Application of a submaximal dose of acetylcholine (500 nM) during the rising phase of the response to thapsigargin caused a 3-4-fold increase in the amplitude of the rise in the cytosolic Ca2+ concentration without any significant alteration of the time course of the response. As thapsigargin alone is capable of mobilizing all releasable Ca2+, this increase in amplitude is most likely the result of inhibition of the Ca2+ extrusion process by acetylcholine.

Acetylcholine↗

PubMed1992

Enhanced superoxide production by alveolar macrophages and air-space cells, airway inflammation, and alveolar macrophage density changes after segmental antigen bronchoprovocation in allergic subjects.

Airway inflammation is a principal determinant of airway responsiveness and function in asthma and allergic diseases. Alveolar macrophages (AM) may contribute to inflammation in multiple ways, including release of reactive oxygen species such as superoxide (SO) anion. We hypothesized that SO production by AM increases after segmental bronchoprovocation (SBP) with relevant antigen and contributes to airway injury. Eight ragweed-sensitive subjects with allergic rhinitis were studied by bronchoalveolar lavage and ragweed SBP to determine the SO production and characteristics of cells recruited after antigen challenge. No significant changes in cell numbers or total protein concentration were observed immediately after antigen challenge. Purification (to greater than 94%) of AM on discontinuous gradients of Percoll revealed significantly increased spontaneous and opsonized-zymosan-driven SO production immediately after antigen challenge. Forty-eight hours later, total air-space cells, AM, eosinophils, and total protein concentration were significantly increased in relationship to antigen dose given. Furthermore, both unfractionated air-space cells and purified AM obtained 48 h after antigen challenge released increased amounts of SO anion in response to activator compared with either cells obtained immediately after SBP or those obtained 48 h after saline challenge. In addition, significant increases in high density AM were also seen 48 h after antigen challenge. These data suggest that AM activation occurs immediately after antigen challenge, and that the late airway response to antigen is characterized by the appearance of high density AM, which have potentiated SO release. The increased oxidative burden thereby produced may contribute to increased airway injury.

Adult↗

PubMedDate not supplied

Silica.

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Homeopathy↗