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The effects of [mu]-opioid receptor agonists on respiratory neurons in the preBoetzinger complex in decerebrate dogs : doctoral thesis

Fakulteti, doktorske disertacije Vrsta gradje
Naslov
The effects of [mu]-opioid receptor agonists on respiratory neurons in the preBoetzinger complex in decerebrate dogs : doctoral thesis / Sanda Mustapić ; mentor Edward J. Zuperku. -
Impresum
Split : S. Mustapić, 2013. -
Materijalni opis
54 lista : ilustr., graf. prikazi ; 30 cm + 1 optički disk. -
Jezik
Engleski
Napomena
Na vrhu nasl. str.: University of Split, School of Medicine.
Bibliografija: listovi 43-49.

SUMMARY
AIM: Systemic administration of q-opioids at clinical doses for analgesia typically decreases respiratory rate.
MORs on preBötC respiratory neurons, the putative kernel of respiratory rhythmogenesis, are potential targets.
The purpose of this study was to determine the contribution of the preBötC MORs to the bradypnea produced in vivo by intravenous administration of clinically relevant infusion rates of remifentanil, a short-acting, potent q-opioid analgesic.
METHODS: In decerebrate dogs, multibarrel micropipettes were used to record preBötC neuronal activity and to eject the opioid antagoinist naloxone (NAL, 0.5 mM), the glutamate agonist D-homocysteic acid (DLH, 20 mM), or the MOR agonist (D-Ala2, N-Me-Phe4, gly-ol5)-enkephalin (DAMGO, 100 qM).
Inspiratory and expiratory durations ( TI and TE) and peak phrenic nerve activity (PPA) were measured from the phrenic neurogram.
The preBötC was functionally identified by its rate altering response (typically tachypnea) to DLH microinjection and neuron composition.

RESULTS: During intravenous remi-induced bradypnea (~60% decrease in central breathing frequency, fB), bilateral injections of NAL into the preBötC did not change TI, TE, fB, and PPA.
Also, NAL picoejected onto single preBötC neurons depressed by intravenous remi had no effect on their discharge.
In contrast, ~60 qg/kg of intravenous NAL rapidly reversed all remi-induced effects.
In a separate group of dogs, microinjections of DAMGO in the preBötC increased fB by 44%, while subsequent intravenous remi infusion more than offset this DAMGO induced tachypnea.

CONCLUSION: These results indicate that q-opioids at plasma concentrations that cause profound analgesia produced their bradypneic effect via MORs located outside the preBötC region.

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