EFFECTS OF PIRENZEPINE, AF-DX-116 AND GALLAMINE ON THE RELEASE OF CATECHOLAMINES FROM THE DOG ADRENAL-GLAND IN RESPONSE TO SPLANCHNIC NERVE-STIMULATION - INTERACTION OF M1-RECEPTORS AND M2-RECEPTORS WITH NICOTINIC RECEPTORS

The present study was undertaken to examine how muscarinic antagonists modify the release of catecholamines evoked by splanchnic nerve stimulation (SNS) from the dog adrenal gland in vivo, in an attempt to elucidate whether muscarinic receptors play a functional role in catecholamine release. Output of epinephrine and norepinephrine was determined from adrenal venous blood by using high-performance liquid chromatography with electrochemical detection. SNS (1 and 3 Hz) produced increases in catecholamine output in a frequency-dependent manner. Intravenous administration of pirenzepine (10-100-mu-g/kg), a selective M1 receptor antagonist, or AF-DX 116 (30-300-mu-g/kg) and gallamine (0.3-3 mg/kg), selective M2 receptor antagonists, did not modify the SNS-induced increases in catecholamine output. C6 (hexamethonium) inhibited the SNS-induced increases in catecholamine output partially in a dose of 1 mg/kg and remarkably in a dose of 10 mg/kg. The combination of C6 (1 mg/kg) with pirenzepine (10-mu-g/kg), AF-DX 116 (30-mu-g/kg) or gallamine (0.3 mg/kg) inhibited the SNS-induced increases in catecholamine output more potently than C6 did by itself. The inhibition by C6 alone was about 50%, but that by each combination reached to about 80%. These results suggest that M2 receptors as well as M1 receptors play a facilitatory role in catecholamine release from the adrenal gland in response to SNS when the nicotinic receptor-mediated mechanism is partially inhibited.