Pharmacological and biochemical comparison of thyrotropin releasing hormone (TRH) and di‐methyl proline‐TRH on pituitary GH<sub>3</sub> cells

McDermott, Alison M.; Wilkin, Graham P.; Dickinson, S.L.

doi:10.1111/j.1476-5381.1990.tb14129.x

Cited by 5 publications

(1 citation statement)

References 33 publications

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“…1D), resulting in an increase in the spontaneous firing rate. This EC 50 value is comparable to those observed in GH 3 cells (McDermott et al 1990), GH 4 C1 cells (Cao et al 1998) and orexin/hypocretin neurons (González et al 2009). The TRH analogue taltirelin also increased the spike frequency with an EC 50 of 44 nM.…”

Section: Discussionsupporting

confidence: 84%

Excitation of locus coeruleus noradrenergic neurons by thyrotropin‐releasing hormone

Ishibashi

Nakahata

Eto

et al. 2009

The Journal of Physiology

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Locus coeruleus (LC) noradrenergic neurons are implicated in a variety of functions including the regulation of vigilance and the modulation of sensory processing. Thyrotropin-releasing hormone (TRH) is an endogenous neuropeptide that induces a variety of behavioural changes including arousal and antinociception. In the present study, we explored whether the activity of LC noradrenergic neurons is modulated by TRH. Using current-clamp recording from isolated rat LC neurons, we found that TRH increased the firing rate of spontaneous action potentials. The TRH action was mimicked by TRH analogues including taltirelin and TRH-gly. In voltage-clamp recording at a holding potential of −50 mV, TRH produced an inward current associated with a decrease in the membrane K + conductance. This current was inhibited by the TRH receptor antagonist chlordiazepoxide. Following inhibition of the pH-sensitive K + conductance by extracellular acidification, the TRH response was fully inhibited. The TRH-induced current was also inhibited by the phospholipase C (PLC) inhibitor U-73122, but not by the protein kinase C inhibitor chelerythrine nor by chelation of intracellular Ca 2+ by BAPTA. The recovery from the facilitatory action of TRH on the spike frequency was markedly inhibited by a high concentration of wortmannin. These results suggest that TRH activates LC noradrenergic neurons by decreasing an acid-sensitive K + conductance via PLC-mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate. The present findings demonstrate that TRH activates LC neurons and characterize the underlying signalling mechanisms. The action of TRH on LC neurons may influence a variety of CNS functions related to the noradrenergic system which include arousal and analgesia.

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Section: Discussionsupporting

confidence: 84%

Excitation of locus coeruleus noradrenergic neurons by thyrotropin‐releasing hormone

Ishibashi

Nakahata

Eto

et al. 2009

The Journal of Physiology

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Thyrotropin releasing hormone (TRH) and a degradation stabilized analogue (RX77368) stimulate phosphoinositide turnover in cultured astrocytes in a regionally specific manner

McDermott

Dickinson²,

Wilkin

1992

Neurochemistry International

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Ventral Horn Neuropeptides Modulate the Release of Noradrenaline from Tissue Slices of Rat Brainstem and Ventral Thoracic Spinal Cord

Fone

Johnson

Putland

et al. 1991

Journal of Neurochemistry

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The release of endogenous noradrenaline (NA) from slices of adult rat brainstem and ventral thoracic spinal cord was investigated using a fixed-volume incubation technique and HPLC with electrochemical detection. Incubation with potassium (15-50 mM) produced a dose-related increase in basal NA release that was calcium dependent. The potassium-evoked release of NA from spinal cord or brainstem slices was potentiated according to dose by preincubation with either (a) the selective alpha 2-adrenoceptor antagonist idazoxan (10(-6)-10(-4) M) or (b) the thyrotrophin-releasing hormone (TRH) analogue RX 77368 (pGlu-His-3,3'-dimethyl ProNH2; 10(-5) and 10(-4) M). Incubation of spinal cord slices with the NA uptake inhibitor maprotiline (1 microM) enhanced the effect of idazoxan but inhibited that of RX 77368. The effects of RX 77368 and potassium alone (15 mM) on NA release from both spinal cord and brainstem slices were reduced to basal levels with tetrodotoxin (10(-7) M). Similarly, preincubation of spinal cord, but not brainstem, slices with the insect neuropeptide proctolin (10(-4) M) significantly attenuated the potassium- or RX 77368-induced release of NA, whereas substance P (3 X 10(-5) and 1 X 10(-4) M) had no effect on either tissue. These results suggest that changes in NA release in the spinal cord and brainstem may mediate some of the actions of neuropeptides in ventral spinal cord, although the peptides may not be acting directly on the noradrenergic nerve terminals in these tissues.

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Pharmacological and biochemical comparison of thyrotropin releasing hormone (TRH) and di‐methyl proline‐TRH on pituitary GH₃ cells

Abstract: 5 These in vitro data suggest that the greater in vivo potency of RX77368 is not the result of enhanced receptor affinity but is more probably due to its greater metabolic stability.

Cited by 5 publications

References 33 publications

Excitation of locus coeruleus noradrenergic neurons by thyrotropin‐releasing hormone

Excitation of locus coeruleus noradrenergic neurons by thyrotropin‐releasing hormone

Thyrotropin releasing hormone (TRH) and a degradation stabilized analogue (RX77368) stimulate phosphoinositide turnover in cultured astrocytes in a regionally specific manner

Ventral Horn Neuropeptides Modulate the Release of Noradrenaline from Tissue Slices of Rat Brainstem and Ventral Thoracic Spinal Cord

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Pharmacological and biochemical comparison of thyrotropin releasing hormone (TRH) and di‐methyl proline‐TRH on pituitary GH3 cells

Abstract: 5 These in vitro data suggest that the greater in vivo potency of RX77368 is not the result of enhanced receptor affinity but is more probably due to its greater metabolic stability.

Cited by 5 publications

References 33 publications

Excitation of locus coeruleus noradrenergic neurons by thyrotropin‐releasing hormone

Excitation of locus coeruleus noradrenergic neurons by thyrotropin‐releasing hormone

Thyrotropin releasing hormone (TRH) and a degradation stabilized analogue (RX77368) stimulate phosphoinositide turnover in cultured astrocytes in a regionally specific manner

Ventral Horn Neuropeptides Modulate the Release of Noradrenaline from Tissue Slices of Rat Brainstem and Ventral Thoracic Spinal Cord

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Pharmacological and biochemical comparison of thyrotropin releasing hormone (TRH) and di‐methyl proline‐TRH on pituitary GH₃ cells