Stimulation of pulmonary J receptors by an enkephalin-analog.
Respiratory and cardiovascular actions of a stable enkephalin-analog (EA), D-met2-pro5-enkephalinamide, were studied in decerebrate male Wistar rats. Injection of a small dose of EA (10 micrograms/kg) into the right atrium produced apnea, bradycardia and hypotension within 1 to 2 sec. These effects lasted for 2 to 4 sec. Apnea was followed by a period of fast and shallow breathing which lasted for 7 to 10 min. The decrease in heart rate and mean blood pressure was 26 +/- 3% (S.E.) and 12 +/- 1.5% (S.E.), respectively. Higher doses of EA used in this study (100,500 and 1,000 micrograms/kg, right atrium) produced similar responses. However, the durations of apnea and fst and shallow breathing and magnitudes of bradycardia and hypotension were greater with the higher doses. Bilateral vagotomy (low in the neck) abolished these effects. These actions are typical of pulmonary J receptor stimulation. Nerve recording experiments in artificially ventilated rats showed that interruption of vagal innervation to the lungs abolished the EA-induced cessation of phrenic nerve activity (apnea), increased frequency of phrenic nerve bursts (fast breathing) and decreased spike activity in each burst (shallow breathing). These results suggested that EA stimulated lung sensory receptors. Of the known lung sensory receptors (stretch, irritant and J. receptors), only pulmonary J receptors are known to produce apnea, bradycardia and hypotension. Direct recordings from pulmonary J receptor fibers in thin filaments of vagus confirmed that EA stimulates these receptors.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004723:Endorphins / Q000494:pharmacology*; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives*; D004745:Enkephalins / Q000494:pharmacology*; D008297:Male; D010791:Phrenic Nerve / Q000187:drug effects; D011651:Pulmonary Artery; D051381:Rats; D012119:Respiration / Q000187:drug effects*; D011984:Sensory Receptor Cells / Q000187:drug effects*; D013268:Stimulation, Chemical
D004723:Endorphins; D004745:Enkephalins; D004744:Enkephalin, Methionine; C021717:enkephalin, Met(2)-ProNH2(5)-