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Neuropharmacology of a slowly adapting type 1 sensory receptor

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PacittiEG_1989redux.pdf (17.26Mb)
Date
1989
Author
Pacitti, Elaine Grace
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Abstract
 
 
The role of the Merkel cell-neurite complex in the transduction process in slowly adapting type 1 {SA1) cutaneous mechanoreceptors is unresolved. One hypothesis, based largely on the ultrastrueture of Merkel cell-neurite complexes, suggests that chemosynaptic transmission occurs between the Merkel cell and its subjacent nerve terminal. This idea was investigated by mechanically stimulating SA1 mechanoreceptors exposed to pharmacologically active agents in several experimental preparations; an in vivo rat model, and in vivo feline isolated hind limb perfusion model and a novel isolated rat skin-nerve preparation.
 
After exposure to the calcium channel blockers Mg2+, Cd2+ and verapamil hydrochloride there was a dose dependent decline in the response of the SA1 mechanoreceptors to mechanical stimulation. Given that an influx of Ca2+ ions is required for stimulus-secretion coupling, these results suppo rt the hypothesis of chemosynaptic transmission.
 
Immunohistochemical studies have shown that a metenkephalin-like substance is associated with the dense cored vesicles in rodent Merkel cells. The idea that metenkephalin was the transmitter substance in rat Merkel cell-neurite complexes was tested using the opiate antagonist naloxone and the agonist met-enkephalin in the isolated rat skin-nerve preparation. Met-enkephalin caused a dose dependent decline in the response of the SAl mechanoreceptors to mechanical stimulation. This effect was antagonised by naloxone, indicating the presence of functional opioid receptors in the SAl sensory receptor. However, this result indicates that met-enkephalin is not the excitatory transmitter substance in rat Merkel cellneurite complexes, though it does have a modulatory role.
 
The results presented in this thesis support the hypothesis that chemosynaptic transmission is involved in the transduction process in the Merkel cell-neurite complex.
 
URI
http://hdl.handle.net/1842/29930
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