Respiratory and cardiovascular effects of the mu-opioid receptor agonist [Lys7]dermorphin in awake rats
| Autor: | Negri, Lucia, Lattanzi, Roberta, Tabacco, F., Melchiorri, Pietro |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Male
Injections Subcutaneous Narcotic Antagonists Receptors Opioid mu Blood Pressure awake rats Hypercapnia respiratory depression Prosencephalon [Lys 7 ]dermorphin Tidal Volume Animals Rats Wistar Injections Intraventricular Naloxone opioids respiratory stimulation blood pressure Rats Quaternary Ammonium Compounds Ritanserin Injections Intravenous Papers Serotonin Antagonists Analgesia Pulmonary Ventilation Oligopeptides |
| Zdroj: | British journal of pharmacology. 124(2) |
| ISSN: | 0007-1188 |
| Popis: | 1. Changes in respiratory variables, arterial blood pressure and heart rate were studied in awake rats after injection of the opioid peptide [Lys7]dermorphin and its main metabolites, [1-5]dermorphin and [1-4]dermorphin. 2. Fifteen minutes after injection, doses of [Lys7]dermorphin producing antinociception (i.c.v., 36-120 nmol; s.c., 0.12-4.7 micromol kg(-1)) significantly increased respiratory frequency and minute volume of rats breathing air or hypoxic inspirates. This respiratory stimulation was reversed to depression by the 5-HT receptor antagonist ritanserin (2 mg kg(-1), s.c.), was blocked by naloxone (0.1 mg kg(-1), s.c.), significantly reduced by the mu1 opioid receptor antagonist naloxonazine (10 mg kg(-1), s.c., 24 h before) but unaffected by peripherally acting opioid antagonist naloxone methyl bromide (3 mg kg(-1), s.c.). Forty five minutes after injection, doses of the peptide producing catalepsy (s.c., 8.3-14.2 micromol kg(-1), i.c.v., 360 nmol) significantly reduced respiratory frequency and volume of rats breathing air and blocked the hypercapnic ventilator response of rats breathing from 4% to 10% CO2. I.c.v. administration of [1-5]dermorphin and [1-4]dermorphin (from 36 to 360 nmol) never stimulated respiration but significantly reduced basal and CO2-stimulated ventilation. Opioid respiratory depression was only antagonized by naloxone. 3. In awake rats, [Lys7]dermorphin (0.1-1 mg kg(-1), s.c.) decreased blood pressure. This hypotensive response was abolished by naloxone, reduced by naloxone methyl bromide and unaffected by naloxonazine. 4. In conclusion, the present study indicates that analgesic doses of [Lys7]dermorphin stimulate respiration by activating central mu1 opioid receptors and this respiratory stimulation involves a forebrain 5-hydroxytryptaminergic excitatory pathway. |
| Databáze: | OpenAIRE |
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