Induction of wet-dog shaking in rats by analogues and metabolites of thyrotrophin-releasing hormone (TRH)

Webster, V.A.D.; Griffiths, E.C.; Slater, P.

doi:10.1016/0167-0115(82)90074-x

Cited by 50 publications

(14 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite this, intrathecal 5,7-DHT did not affect the wet-dog shakes or the forepaw-licking produced by intrathecal TRH analogue administration, supporting the proposal that these behaviours are not mediated by bulbospinal 5-HTergic neurones. In accordance with this proposal previous work suggests that the brain area involved in mediating 5-HT-and TRH-induced wet-dog shake behaviour is in the medial brainstem, between the colliculi and the anterior commissure, as lesions in this region reduce the shaking produced by 5-hydroxytryptophan (5-HTP) and water immersion (Wei et al, 1973;Bedard & Pycock, 1977;Wei, 1981), while micro-injection of TRH into the medial brainstem (Wei, 1981) or the area of the locus coeruleus (Kalivas & Horita, 1981;Webster et al, 1982) caused vigorous wet-dog shakes. Since intrathecal 5,7-DHT significantly enhanced the 5-MeODMTbut had no effect on the TRH analogue-induced shaking, the 5-HT-and TRH-induced wet-dog shakes may be mediated by separate 5-HTergic pathways.…”

Section: Behaviours Produced By Intrathecal Cg 3509 Administrationmentioning

confidence: 99%

Involvement of 5‐HT₂ receptors in the behaviours produced by intrathecal administration of selected 5‐HT agonists and the TRH analogue (CG 3509) to rats

Fone

Johnson

Bennett

et al. 1989

British J Pharmacology

View full text Add to dashboard Cite

1 The behavioural effects of the intrathecal injection of a thyrotrophin-releasing hormone (TRH) analogue L-orotyl-L-histidyl-prolineamide (CG 3509, 0.5 /g), the non-selective 5-HT, and 5-HT2 receptor agonist 5-methoxy-N,N'-dimethyltryptamine (5-MeODMT, 2-100pg) and the selective 5-HT2 receptor agonist 2,5-dimethoxy-a,4-dimethyl-benzene ethamine hydrochloride (DOM, 2-25 ug) were compared with the response of systemically administered 5-MeODMT (2 mg kg-1, i.p.) in rats, to establish whether the agonist-induced behaviours were mediated by bulbospinal 5-HT, or 5-HT2 receptors. 2 Intrathecal injection of 5-MeODMT or DOM produced dose-related back muscle contractions (a previously undocumented behaviour) and wet-dog shakes which were both markedly attenuated by ritanserin pretreatment (1 mg kg 1, i.p.) indicating the involvement of 5-HT2 receptors. In contrast, reciprocal forepaw treading, flat body posture and Straub-tail were evoked by 5-MeODMT but not by DOM indicating that these behaviours were not produced by 5-HT2 receptor activation alone. However, as ritanserin pretreatment reduced the reciprocal forepaw treading induced by intrathecal 5-MeODMT, this behaviour may be facilitated by 5-HT2 receptor activation.3 Intrathecal 5,7-dihydroxytryptamine (5,7-DHT, 2 x 150pg) treatment decreased thoraco-lumbar spinal cord 5-HT (-95%) and potentiated the back muscle contractions produced by intrathecal DOM injection without altering the wet-dog shake behaviour. None of the components of the 5-HT syndrome produced by 5-MeODMT (2mgkg-1, i.p.), with the exception of a small increase in wet-dog shakes, was significantly altered by intrathecal 5,7-DHT (which reduced thoraco-lumbar spinal cord 5-HT by 84%). Taken together these data suggest that the only 5-HT agonist-induced behaviour mediated by the activation of 5-HT2 receptors located postsynaptic to bulbospinal 5-hydroxytryptaminergic (5-HTergic) neurones was back muscle contractions. 4 The wet-dog shake and forepaw licking behaviors produced by intrathecal CG 3509 (0.5 Mg) were attenuated when ritanserin was administered intrathecally 30 min before, but not when it was given at the same time as CG 3509 and neither behaviour was altered by intrathecal 5,7-DHT. This suggests that bulbospinal 5-HTergic neurones are not involved in the production of these TRH analogue-induced behaviours and that the 5-HT2 receptors which mediate these behaviours are not located in the spinal cord.

show abstract

Section: Behaviours Produced By Intrathecal Cg 3509 Administrationmentioning

confidence: 99%

Involvement of 5‐HT₂ receptors in the behaviours produced by intrathecal administration of selected 5‐HT agonists and the TRH analogue (CG 3509) to rats

Fone

Johnson

Bennett

et al. 1989

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…TRH-OH has been detected by radioimmunoassay in rat brain [26] and human urine [5], and induces wet-dog shak ing in rats in a similar way to TRH after intracerebroventricular injection [12] and direct application to the peri aqueductal grey region [79]. This property may reflect the relative stability of TRH-OH in brain tissue, since it is only slowly degraded to its constituent amino acids [33] and per haps its ability to be reamidated to TRH itself [79]. Cyclo(His-Pro) has been shown to have many effects on the brain where it is present in much higher concentrations than TRH and has several properties related or unrelated to TRH [58,59].…”

Section: Trh Somatostatin and Lh-rhmentioning

confidence: 99%

Biotransformation of Neuropeptides

Griffiths¹,

McDermott²

1984

Neuroendocrinology

View full text Add to dashboard Cite

The ability of neuropeptides to act as precursors for smaller, biologically active fragments is discussed in terms of their biotransformation. This process may involve cleavage of the parent peptide by peptidase enzymes to produce shorter polypeptides with defined biological activity, though other enzymic processes such as sulphation and acetylation may be implicated. Detection of the specific fragments in vivo, their release, receptor-binding and biological actions may confirm biotransformation of the parent peptide. Control of biotransformation will depend upon the localization, both regional and subcellular, and the specificity of the enzymes involved. This process may give an additional degree of flexibility to the biological effects of neuropeptides.

show abstract

“…Although similarities between the brain and pituitary receptors have been noted (4), attempts have been made to produce analogues to structurally dissociate the endocrine and neurotransmitter actions of TRH (5). [NE 3 Me-His]-TRH has been shown to be about eight times more active than TRH in stimulating the release of thyrotrophin (TSH) from the pituitary (6), whilst equipotent or less potent in its CNS actions (7). The increase in activity of some TRH analogues has been generally attributed to (a) Chemical structures of thyrotrophin-releasing hormone (TR€:) and some of its analogues.…”

mentioning

confidence: 99%

Comparative conformation‐activity relationships for hormonally‐ and centrally‐acting TRH analogues

Ward¹,

Finn²,

Griffiths

et al. 1987

International Journal of Peptide and Protein Research

View full text Add to dashboard Cite

Empirical energy calculations have been applied to a series of thyrotrophin‐releasing hormone (TRH) analogues in an attempt to incorporate the conformational parameter into traditional Quantitative Structure‐Activity Relationships (QSAR). A search was made of the potential surface of each analogue using a SIMPLEX technique coupled with a model representing solvent effects as a dielectric continuum. Conformers of TRH can be described in terms of the distance between the pyroglutamyl, imidazole and prolyl rings, and presented as two‐dimensional descriptor coordinates using multidimensional scaling. This process was repeated for stable and metastable conformers of all the TRH analogues investigated and correlated with experimental data on receptor affinity, relative stability and biological potency of the analogues. The results obtained suggest that modifications to the TRH structure can lead to greater potency in addition to improved stability, and that providing the appropriate theoretical approach is taken, it is possible to apply QSAR‐based design procedures to conformationally‐flexible drugs.

show abstract

Induction of wet-dog shaking in rats by analogues and metabolites of thyrotrophin-releasing hormone (TRH)

Cited by 50 publications

References 10 publications

Involvement of 5‐HT₂ receptors in the behaviours produced by intrathecal administration of selected 5‐HT agonists and the TRH analogue (CG 3509) to rats

Involvement of 5‐HT₂ receptors in the behaviours produced by intrathecal administration of selected 5‐HT agonists and the TRH analogue (CG 3509) to rats

Biotransformation of Neuropeptides

Comparative conformation‐activity relationships for hormonally‐ and centrally‐acting TRH analogues

Contact Info

Product

Resources

About

Induction of wet-dog shaking in rats by analogues and metabolites of thyrotrophin-releasing hormone (TRH)

Cited by 50 publications

References 10 publications

Involvement of 5‐HT2 receptors in the behaviours produced by intrathecal administration of selected 5‐HT agonists and the TRH analogue (CG 3509) to rats

Involvement of 5‐HT2 receptors in the behaviours produced by intrathecal administration of selected 5‐HT agonists and the TRH analogue (CG 3509) to rats

Biotransformation of Neuropeptides

Comparative conformation‐activity relationships for hormonally‐ and centrally‐acting TRH analogues

Contact Info

Product

Resources

About

Involvement of 5‐HT₂ receptors in the behaviours produced by intrathecal administration of selected 5‐HT agonists and the TRH analogue (CG 3509) to rats

Involvement of 5‐HT₂ receptors in the behaviours produced by intrathecal administration of selected 5‐HT agonists and the TRH analogue (CG 3509) to rats