High affinity 2-[125I]-iodomelatonin binding has been demonstrated in cerebral arteries of rat (46,53,54), non-human primates (48), and humans (48). Initially, binding was found in arteries associated with the circle of Willis, e.g. anterior and middle cerebral arteries (53). Subsequently, 2-[125I]-iodomelatonin binding was observed in inferior cerebellar, vertebral, spinal, and internal carotid arteries as well (48), suggesting a widespread distribution of melatonin receptors in the cerebral circulation. Interestingly, the density of 2-[125I]-iodomelatonin binding sites in rat cerebral arteries is modified during the female estrous cycle (46), postnatal development (38) and in genetic hypertension (54).
Saturation analysis of binding to rat anterior cerebral arteries indicated two affinity states for 2-[125I]-iodomelatonin (Kd of 13 pM and 823 pM) and a sensitivity to guanine nucleotides (9). In slices of rat cerebral arteries, melatonin inhibited forskolin-stimulated cyclic AMP production via a pertussis toxin sensitive mechanism (9). These findings are consistent with the characteristics of known Gi/o-protein coupled mela-tonin receptors, but do not indicate the identity of the receptor subtype(s) involved (17,34).
The presence of melatonin receptor subtypes is supported by recent demonstrations of appropriate receptor mRNA in cerebrovascular tissue. Using RT-PCR, cDNA for the mt1 receptor subtype could be amplified from human middle cerebral and cortical arteries (37). Expression of both mt1 and MT2 receptor mRNA has been detected in rat and human cerebral arteries using RT-PCR and in situ hybridization (40).
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