Sites Of Action Of Melatonin 41 Melatonin Receptors

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In situ autoradiography using 2-(125I)iodomelatonin as a ligand has been used to map the distibution of putative melatonin receptors in the ovine brain and pituitary gland with the aim of identifying target sites for the action of melatonin (Figure 2). Specific, high affinity binding of melatonin has been demonstrated in many sites in the hypothalamus, limbic system and brain, with highest levels of binding in the pars tuber-alis of the pituitary gland (5,20). Using in situ hybridization with a specific probe for the melatonin receptor (mtl receptor) melatonin receptor gene expression has been demonstrated in the pars tuberalis/zona tuberalis of the ovine pituitary (62,69), but not in the brain sites indicated by binding studies. This may reflect a lower of expression in the neural sites, or the presence of another form of receptor. The latter possibility is indicated by failure to find a transcript corresponding to the mt1 receptor in

Melatonin Receptor Brain

Figure 2. 2-(125I)Iodomelatonin binding in the ovine brain and pituitary gland as revealed by in situ autoradiography. The putative areas involved in the photoperiodic regulation of gonadotrophin secretion (1) and PRL secretion (2) are indicated (see text). Abbreviations: H—hippocampus. OC — optic chiasma, MB mam-millary body, MT—medial thalamus, PD—pars distalis. Data from Helliwell & Williams (20) are reproduced by permission.

Figure 2. 2-(125I)Iodomelatonin binding in the ovine brain and pituitary gland as revealed by in situ autoradiography. The putative areas involved in the photoperiodic regulation of gonadotrophin secretion (1) and PRL secretion (2) are indicated (see text). Abbreviations: H—hippocampus. OC — optic chiasma, MB mam-millary body, MT—medial thalamus, PD—pars distalis. Data from Helliwell & Williams (20) are reproduced by permission.

hypothalamic RNA extracts amplified by RT PCR (P. Morgan, personal communication). The affinity of G-protein coupled receptors, including the melatonin receptor, is altered in the presence of guanine nucleotides resulting in an apparent drop in receptor number (55). This response can be demonstrated for 2-(125I)iodomelatonin binding the pars tuberalis but not for binding in the hippocampus and other areas of the brain (57,69) consistent with the view that there is a intrinsic difference between the G-protein coupled melatonin receptor in the pars tuberalis and the putative melatonin receptor(s) in the areas of the ovine brain.

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