Calcitonin gene-related peptide (CGRP) content and CGRP receptor binding sites in discrete forebrain regions of alcohol-preferring vs. -nonpreferring rats, and high alcohol-drinking vs. low alcohol-drinking rats

The distribution of amylin receptors (125I-labelled rat amylin) in brains of rat and monkey were mapped and compared with the distribution of receptors for calcitonin (CT) (125I-labelled salmon CT) and calcitonin gene related peptide (CGRP) (rat, 125I-labelled rat CGRPα; monkey, 125-labelled human CGRPα). In rat, amylin receptors were discretely distributed with the highest receptor densities found in mid-caudal accumbens nucleus, parts of the bed nucleus of the stria terminalis, amygdala, and hypothalamus. Moderate to high densities of binding also occurred in the area postrema, subfornical organ, vascular organ of the lamina terminalis, locus ceruleus, dorsal raphe, and caudal solitary tract nucleus. In monkey, the distribution of amylin binding sites was similar, although the highest densities of receptors were in the hypothalamus, with relatively fewer sites present in the accumbens nucleus. In rat, the distribution of amylin receptors formed a subset of the receptor distributions for 125I-labelled salmon CT and 125I-labelled rat CGRPα. In contrast, in monkey, although the amyiin receptors again formed a subset of the binding sites identified with 125I-labelled salmon CT, mere was very little overlap with the pattern of CGRP receptor distribution. This suggests that the specificity profile of amylin receptors in primates differs from that of amylin receptors in the rat, with CGRPα having relatively lower affinity for the primate amylin receptors.Key words: amylin, calcitonin, calcitonin gene related peptide, receptor, rat, monkey.

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Calcitonin gene-related peptide receptors in rat trigeminal ganglion do not control spinal trigeminal activity

Journal of Neurophysiology ◽

10.1152/jn.00167.2011 ◽

2012 ◽

Vol 108 (2) ◽

pp. 431-440 ◽

Cited By ~ 20

Author(s):

Oana Covasala ◽

Sören L. Stirn ◽

Stephanie Albrecht ◽

Roberto De Col ◽

Karl Messlinger

Keyword(s):

Trigeminal Ganglion ◽

Dura Mater ◽

Calcitonin Gene Related Peptide ◽

Afferent Input ◽

Nitric Oxide Donor ◽

Cgrp Receptor ◽

Related Peptide ◽

Trigeminal Neurons ◽

Calcitonin Gene ◽

Evoked Activity

Calcitonin gene-related peptide (CGRP) is regarded as a key mediator in the generation of primary headaches. CGRP receptor antagonists reduce migraine pain in clinical trials and spinal trigeminal activity in animal experiments. The site of CGRP receptor inhibition causing these effects is debated. Activation and inhibition of CGRP receptors in the trigeminal ganglion may influence the activity of trigeminal afferents and hence of spinal trigeminal neurons. In anesthetized rats extracellular activity was recorded from neurons with meningeal afferent input in the spinal trigeminal nucleus caudalis. Mechanical stimuli were applied at regular intervals to receptive fields located in the exposed cranial dura mater. α-CGRP (10−5 M), the CGRP receptor antagonist olcegepant (10−3 M), or vehicle was injected through the infraorbital canal into the trigeminal ganglion. The injection of volumes caused transient discharges, but vehicle, CGRP, or olcegepant injection was not followed by significant changes in ongoing or mechanically evoked activity. In animals pretreated intravenously with the nitric oxide donor glyceryl trinitrate (GTN, 250 μg/kg) the mechanically evoked activity decreased after injection of CGRP and increased after injection of olcegepant. In conclusion, the activity of spinal trigeminal neurons with meningeal afferent input is normally not controlled by CGRP receptor activation or inhibition in the trigeminal ganglion. CGRP receptors in the trigeminal ganglion may influence neuronal activity evoked by mechanical stimulation of meningeal afferents only after pretreatment with GTN. Since it has previously been shown that olcegepant applied to the cranial dura mater is ineffective, trigeminal activity driven by meningeal afferent input is more likely to be controlled by CGRP receptors located centrally to the trigeminal ganglion.

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