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Query: UNIPROT:P20396 (Thyrotropin-releasing hormone)
 559 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thyrotropin-releasing hormone prohormone contains five copies of the thyrotropin-releasing hormone progenitor sequence Gln-His-Pro-Gly, each flanked by pairs of basic amino acids and separated by intervening sequences (connecting peptides). Using a perifusion system for rat hypothalamic slices, we have studied the ionic mechanisms underlying the release of two connecting peptides originating from the thyrotropin-releasing hormone precursor: prepro-thyrotropin-releasing hormone-(160-169) (Ps4) and prepro-thyrotropin-releasing hormone-(178-199) (Ps5). Quantification of these two peptides in the effluent fluid was performed using sensitive and highly specific radioimmunoassay procedures. Reverse phase high performance liquid chromatography analysis of the effluent perifusate showed that released peptides co-eluted with synthetic Ps4 and Ps5. The secretion of Ps4 and Ps5 was stimulated by depolarizing agents such as (i) high potassium concentrations, (ii) ouabain, an Na+/K(+)-ATPase inhibitor, and (iii) veratridine, a stimulator of voltage-operated Na+ channels. The response to potassium (70 mM) was not affected by the specific Na+ channel blocker tetrodotoxin. The K+ channel blocker tetraethylammonium did not modify K(+)-evoked release of Ps4 and Ps5. These data suggest that voltage-operated Na+ channels are not involved in the stimulatory effect of high K+ on the release of Ps4 and Ps5. The lack of effect of picrotoxin, a Cl- channel blocker, on the secretion of the connecting peptides indicates that chloride ions play a minor role in the release process. In contrast, deprivation of Ca2+ in the perifusion medium suppressed K(+)-evoked release of the two peptides, indicating that voltage-operated Ca2+ channels are implicated in the release process. Taken together, the present results show that non-thyrotropin-releasing hormone peptides originating from the thyrotropin-releasing hormone precursor are secreted by mediobasal hypothalamic fragments. The release of these peptides is stimulated by depolarization through a calcium-dependent process. These data indicate that Ps4 and Ps5 may be released at the level of the median eminence into the portal circulation, suggesting that these peptides may play a role in the control of anterior pituitary cells.
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PMID:Release of pro-thyrotropin-releasing hormone connecting peptides PS4 and PS5 from perifused rat hypothalamic slices. 172 91

In the female rat immunoreactive prolactin (IR-PRL) has been identified in the hypothalamus and in other brain regions. Brain IR-PRL is not of pituitary origin and, based on polyacrylamide gel electrophoresis and peptide mapping, shares a high degree of sequence homology with its pituitary counterpart. We have previously shown that hypothalamic tissue can release IR-PRL in vitro when depolarized by potassium. In this study, we examined the release of IR-PRL from hypothalami obtained from intact and ovariectomized rats and incubated in the presence of veratridine (an alkaloid which depolarizes excitable membranes), angiotensin II, or thyrotropin-releasing hormone. Hypothalamic tissue spontaneously released IR-PRL, and this release was significantly increased by veratridine or angiotensin II in a dose-dependent manner. The specificity of the angiotensin-II-evoked IR-PRL release was demonstrated by the inhibitory effect of saralasin, an angiotensin II receptor antagonist, on hypothalamic IR-PRL release. Thyrotropin-releasing hormone (100 microM) had no effect on hypothalamic IR-PRL release. Ovariectomy decreased hypothalamic IR-PRL content and IR-PRL release in response to veratridine and angiotensin II. The effect of estradiol on hypothalamic IR-PRL content and release was also examined by obtaining hypothalami from ovariectomized rats injected with estradiol (1 microgram/day) or vehicle for 5 days. When compared with vehicle injected rats, administration of estradiol significantly increased the hypothalamic IR-PRL content (46 +/- 4 vs. 81 +/- 16 ng/mg protein).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stimulation of hypothalamic prolactin release by veratridine and angiotensin II in the female rat: effect of ovariectomy and estradiol administration. 175 81

1. High potassium (50 mM)-evoked acetylcholine (ACh) release from rat basal forebrain slices under conditions without an exogenous choline supply was determined using a radioimmunoassay for ACh. 2. A consistent amount of ACh release was observed at each repetitive stimulation and ACh content in brain slices was not altered by potassium stimulations. These results indicate the existence of a large intracellular releasable ACh store, which is independent of new synthesis from exogenous choline. 3. Atropine, even at a concentration of 10(-6) M, did not affect the potassium-evoked ACh release. Thus, modulation of ACh release by the muscarinic autoreceptor was not revealed under the conditions employed. 4. Thyrotropin-releasing hormone (TRH, 10(-4) M) caused a slight and statistically insignificant increase in potassium-evoked ACh release. DN-1417, a TRH analogue, at a concentration of 10(-4) M significantly increased potassium-evoked ACh release. These findings indicate that DN-1417 is able to enhance ACh output independently of ACh synthesis from exogenous choline.
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PMID:Effects of TRH and DN-1417 on high potassium-evoked acetylcholine release from rat basal forebrain slices determined directly by radioimmunoassay. 256 49

Thyrotropin-releasing hormone (TRH) induces rapid and transient conversion of protein kinase C (Ca2+/phospholipid-dependent enzyme) from a soluble to a particulate-bound form in GH4C1 rat pituitary cells. Ionomycin (200 nM), a calcium ionophore, had no effect by itself on the subcellular distribution of protein kinase C. However, pretreatment of the cells with 200 nM ionomycin inhibited by greater than 50% the ability of TRH to cause translocation of protein kinase C from the cytosol to the particulate cell fraction. Inhibition by ionomycin required that the cells be incubated with the ionophore for at least 10 s before TRH addition. Ionomycin pretreatment did not alter the kinetics of TRH-induced protein kinase C redistribution. Incubation of the cells with 43 mM potassium prior to TRH addition almost completely reversed the inhibition induced by ionomycin. We propose that the mechanism by which ionomycin attenuates TRH action on protein kinase C may involve the capacity of the ionophore to empty the intracellular calcium reservoir which normally releases calcium into the cytosol in response to TRH. Our result provides evidence that the rise in intracellular calcium, which accompanies diacylglycerol formation following TRH action on polyphosphatidylinositide hydrolysis, may be required to achieve maximal conversion of protein kinase C to its presumed active, membrane-bound form in these cells.
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PMID:Ionomycin inhibits thyrotropin-releasing hormone-induced translocation of protein kinase C in GH4C1 pituitary cells. 311 Jan 61

Thyrotropin-releasing hormone (TRH) has been recognized as a neuromodulator in several CNS regions, including the thoracolumbar spinal cord where an influence on cardiovascular autonomic function has been proposed. To identify the cellular mechanisms involved in the latter, whole cell patch-clamp recordings were obtained from 52 thoracolumbar lateral horn cells, including 17 sympathetic preganglionic neurons (SPNs), in spinal cord slices from neonatal rat (11-21 days). Under current clamp, bath applications of TRH (1-20 microM) induced a slowly rising and prolonged membrane depolarization in eight of nine cells tested. Under voltage clamp (holding potential -65 mV), 33 of 37 tested cells displayed a TRH-induced, tetrodotoxin-resistant inward current that was associated with either a reduction or an increase in membrane ion conductances. Current-voltage (I-V) relationships in 28 cells suggested two conductances. In 9 cells the current reversed at about -107 mV; in 10 cells the I-V lines remained parallel, whereas in 9 cells the current reversed at around -40 mV. In three of three cells, addition of 2 mM barium was associated with an inward current, and the TRH-induced inward current was also suppressed, suggesting the presence of a resting barium- and TRH-sensitive potassium conductance. A residual barium-insensitive conductance was seen to reverse near -40 mV. Intracellular dialysis with guanosine 5'-o-(3-thiotriphosphate) significantly enhanced the duration of the TRH effect, indicating that G protein activation participates in the TRH response. These observations not only reveal a direct, G-protein-mediated depolarizing action of TRH on neonatal rat SPNs and lateral horn cells but also imply that two separate conductances may be involved in the TRH responses in some neurons.
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PMID:Two conductances mediate thyrotropin-releasing-hormone-induced depolarization of neonatal rat spinal preganglionic and lateral horn neurons. 931 Apr 57

Previous studies have shown that intronic peptide sequences in the prohormone for thyrotropin-releasing hormone (TRH) have physiological actions on pituitary hormone secretion. The aim of this investigation was to examine the effect of the cryptic peptides, prothyrotropin- releasing hormone(178-199) (ProTRH(178-199)) and ProTRH(186-199), on prolactin (PRL) release from the anterior pituitary. Perifusion studies were performed with anterior pituitaries obtained from individual adult male Sprague Dawley rats at 70 90 d of age. Perifusate was collected in 5-min fractions for 25 min prior to peptide administration and for 60 min afterward. Pituitaries were perifused with a single 5 min pulse of either 2, 10, or 40 nM concentrations (peak pulse) of each peptide or the vehicle. Sixty minutes after peptide administration, a 200 mM pulse of potassium chloride was delivered to check tissue viability. Prolactin was measured in the perifusate by radioimmunoassay. Results showed that both peptides induced a significant long-term suppression of prolactin secretion that was still evident at 60 min after peptide exposure. ProTRH(186-199) was similar to ProTRH(178-199) in suppressing prolactin release at the 2 and 40 nM dose, suggesting that the amino acid sequence necessary for prolactin inhibition is contained within the smaller peptide fragment. These data indicate that a cryptic sequence within the proTRH peptide can have biological activity at the level of the anterior pituitary gland in regulating prolactin secretion.
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PMID:Inhibition of prolactin secretion from the male rat anterior pituitary by cryptic sequences of prothyrotropin releasing hormone, ProTRH178-199 and ProTRH186-199. 1262 32

Thyroliberin is a neuropeptide with marked respiratory activity. The neuronal mechanisms underlying this activity were addressed in experiments on transverse slices of brainstem from adult rats in conditions of membrane potential clamping to study effect effects of thyroliberin (10 nM) on the potassium A-current in neurons of two areas of the respiratory center--the ventrolateral areas of the solitary tract nucleus and the pre-Betzinger complex. The A-current, seen in all study neurons in the respiratory center, was partially and reversibly blocked by thyroliberin. A significant reduction in the amplitude of the current was accompanied by an increase in the inactivation constant. The effect of thyroliberin on the amplitude of the A-current was analogous to that of 5 mM 4-aminopyridine. These results show that the stimulatory effects of thyroliberin at the level of respiratory center neurons is at least partly explained by its ability to block the potassium A-current.
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PMID:Thyroliberin blocks the potassium A-current in neurons in the respiratory center of adult rats in vitro. 1603 4

Excess excitatory amino acid release is involved in pathways associated with seizures and neurodegeneration. Thyrotropin-releasing hormone (TRH; protirelin), a brain-derived tripeptide, has shown efficacy in the treatment of such disorders, yet its mechanism of neuroprotection is poorly understood. Using superfused hippocampal slices, we tested the hypothesis that TRH could inhibit evoked glutamate/aspartate release in vitro. Rat hippocampal slices were first equilibrated in oxygenated Krebs buffer (KRB) (120 min) then superfused for 10 min with KRB (control), or KRB containing 0.1, 1, or 10 microM TRH respectively, prior to and during 5 min depolarization with high potassium KRB (50 mM [K(+)] +/- TRH). Fractions (1 min) were collected during the 5 min stimulation and for an additional 10 min thereafter and analyzed for glutamate and aspartate by HPLC. TRH had no effect on baseline glutamate/aspartate release, while all three TRH doses significantly (P < 0.05) inhibited peak 50 mM [K(+)]-stimulated glutamate/aspartate release, and glutamate remained below control (P < 0.05) at 15 min post stimulation. A 5 min pulse of TRH (10 microM) had no affect on basal glutamate/aspartate release, whereas the TRH pre-pulsed slices failed to release glutamate/aspartate by [K(+)]-stimulation given 15 min later. These results are the first to show a potent and prolonged inhibitory effect of TRH on evoked glutamate/aspartate release in vitro. These initial studies suggest that exogenous and/or endogenous TRH may function, in part, to modulate excess glutamate release in specific CNS loci. Additional studies are in progress to fully understand the mechanism of this potent effect of TRH and its implication in various CNS disorders.
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PMID:Thyrotropin-releasing hormone (protirelin) inhibits potassium-stimulated glutamate and aspartate release from hippocampal slices in vitro. 1605 93

The histaminergic tuberomamillary nucleus (TMN) controls arousal and attention, and the firing of TMN neurons is state-dependent, active during waking, silent during sleep. Thyrotropin-releasing hormone (TRH) promotes arousal and combats sleepiness associated with narcolepsy. Single-cell reverse-transcription-PCR demonstrated variable expression of the two known TRH receptors in the majority of TMN neurons. TRH increased the firing rate of most (ca 70%) TMN neurons. This excitation was abolished by the TRH receptor antagonist chlordiazepoxide (CDZ; 50 mum). In the presence of tetrodotoxin (TTX), TRH depolarized TMN neurons without obvious change of their input resistance. This effect reversed at the potential typical for nonselective cation channels. The potassium channel blockers barium and cesium did not influence the TRH-induced depolarization. TRH effects were antagonized by inhibitors of the Na(+)/Ca(2+) exchanger, KB-R7943 and benzamil. The frequency of GABAergic spontaneous IPSCs was either increased (TTX-insensitive) or decreased [TTX-sensitive spontaneous IPSCs (sIPSCs)] by TRH, indicating a heterogeneous modulation of GABAergic inputs by TRH. Facilitation but not depression of sIPSC frequency by TRH was missing in the presence of the kappa-opioid receptor antagonist nor-binaltorphimine. Montirelin (TRH analog, 1 mg/kg, i.p.) induced waking in wild-type mice but not in histidine decarboxylase knock-out mice lacking histamine. Inhibition of histamine synthesis by (S)-alpha-fluoromethylhistidine blocked the arousal effect of montirelin in wild-type mice. We conclude that direct receptor-mediated excitation of rodent TMN neurons by TRH demands activation of nonselective cation channels as well as electrogenic Na(+)/Ca(2+) exchange. Our findings indicate a key role of the brain histamine system in TRH-induced arousal.
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PMID:Excitation of histaminergic tuberomamillary neurons by thyrotropin-releasing hormone. 1935 73