TRH Interactions with Cholinergic Mechanisms and Consequent Therapeutic Implications
Subsequent to the claim that thyrotropin-releasing hormone (TRH; pyroglutamyl-histidyl-proline amide) was effective in the treatment of depression (Prange and Wilson, 1972) and the demonstration that TRH enhanced the stimulant properties of L-dopa in mice (Plotnikoff et al., 1972), a great deal of experimental work has been devoted to elucidating both the basic pharmacological properties of this small peptide and its underlying mode of action. To date, a unifying hypothesis that would satisfactorily account for the multiple and unique actions of exogenously administered TRH is not apparent. Similarly, the functional significance of endogenous, extrahypothalamic TRH, which is found in both mammalian and nonmammalian species, is largely a matter of conjecture. However, with continued research in a variety of experimental preparations an unusual property, which appears to underlie many of the pharmacological effects of TRH, has emerged; namely that TRH, at all levels of the neuraxis and in a unique fashion, appears to facilitate cholinergic transmission via a unique action on central cholinergic neurons. The evidence for these phenomena and consequent therapeutic indications are summarized below.
KeywordsCholine Uptake Antimuscarinic Agent Cholinergic Mechanism Cerebral Cortical Neuron Vagal Efferents
Unable to display preview. Download preview PDF.
- Horita, A., Carino, M. A., and Chesnut, R. M., 1976, Influence of thyrotropin-releasing hormone (TRH) on drug induced narcosis and hypothermia in rabbits, Psychopharmacol. Bull. 49:57.Google Scholar
- Nagai, Y., Narumi, S., Nagawa, Y., Sakurada, O., Ueno, H., and Ishii, S., 1980, Effect ofthy-rotropin-releasing hormone (TRH) on local cerebral glucose utilization, by the autoradiographic 2-deoxy[14C]glucose method, in conscious and phenobarbitalized rats, J. Neurochem. 35:963.PubMedCrossRefGoogle Scholar
- Phillis, J. W. (ed.), 1970, The Pharmacology of Synapses, Pergamon Press, Elmsford, N.Y.Google Scholar
- Prange, A. J., and Wilson, I. C., 1972, Thyrotropin-releasing hormone (TRH) for the immediate relief of depression: A preliminary report, Psychopharmacologia 26:82.Google Scholar
- Veber, D. F., Holly, F. W., Varga, S. L., Hirschmann, R., Nutt, R. F., Lotti, V. J., and Porter, C. C., 1976, The dissociation of hormonal and CNS effects in analogs of TRH, Proceedings 14th European Peptide Symposium (A. Loffet, ed.), pp. 167–172, University of Brunds Press, Belgium.Google Scholar
- Yarbrough, G. G., Haubrich, D. R., and Schmidt, D. E., 1978, Thyrotropin releasing hormone (TRH) and MK-771 interactions with CNS cholinergic mechanisms, in: Iontophoresis and Transmitter Mechanisms in the Mammalian Central Nervous System (R. Ryall and J. S. Kelly, eds.), pp. 136–138, Elsevier/North-Holland, Amsterdam.Google Scholar