Proceedings of The Physiological Society
Kings College London (2005) J Physiol 565P, C166
The tachypnoea evoked by non-peptidic delta opiate receptor agonists, but not that due to chest compression, is blocked by Naltrindole in the anaesthetised rabbit
Sears, Thomas A.; Banks, Duncan ;
1. Department of Physiology, GKT, King's College London, London, United Kingdom. 2. Department of Biological Sciences, The Open University, Milton Keynes, United Kingdom.
Non-peptidic δ-opioid receptor agonists offer the prospect of analgesia free from the respiratory depression due to μ-receptor agonists (as with oral SB 235863 in the rat, Pozzi et al. 1998). Given to anaesthetised rabbits I.V., SB 235863 actually evoked a tachypnoea abolished by cervical vagotomy (Sears & Banks, 2002) as now described for two other δ agonists. New Zealand white rabbits (2.0-3.0 kg) were anaesthetised with Na pentobarbitone (40-60 mg/kg I.P.) and subsequently by constant I.V. infusion (6-8 mg/kg/h). Carotid BP was measured and ear and jugular veins cannulated for giving fluids and drugs. Silver ball electrodes sealed 3.0 mm apart on a plastic strip recorded the EMG from the abdominal surface of the diaphragm; tracheal airflow and alveolar CO2 were also measured. An oil-filled syringe on a rack and pinion was lowered so that its plunger applied a steady force to the sternum as detected by syringe pressure. Signals were acquired via a CED 1401Plus and Spike 2v5 software. At 0.1 mg/kg I.V., Pfizer UK321130 evoked a short latency tachypnoea of more than 5 min duration (Fig. 1A), a 0.75% fall in alveolar CO2 and small increases in HR and mean BP (10 mmHg). Pressure on the sternum evoked an abrupt increase in instantaneous respiratory rate (20-40/min, not shown). After 30 min, the δ-opioid receptor antagonist Naltrindole (1.0 mg/kg, I.V.) was given. Five minutes later, the respiratory responses to the δ agonist were completely blocked (Fig. 1B), whereas those due to chest compression persisted (Fig. 1C); similar results were obtained with SNC80. Cervical vagotomy abolished the tachypnoea evoked by Pfizer UK321130 and the other agonist tested (SNC80). Although tachypnoea also occurred with higher doses of the agonists, slowing and eventually apnoea supervened (in some cases partially reversed by Naloxone or sternal pressure) and brief latency falls in HR and BP invariably occurred. The actions of these δ-opioid agonists given I.V. are complex; nevertheless the differential effects of the antagonist Naltrindole and vagotomy suggest that different groups of receptors mediate the tachypnoea; further studies are needed to identify their nature and location.
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