Effects of salmeterol on muscarinic inhibition of adenylyl cyclase in bovine trachealis cells.
The goal was to assess whether salmeterol, a potent and long-acting beta-2-adrenergic agonist used in the treatment of asthma, also has non-beta-2-adrenergic effects on the stimulation or inhibition of adenylyl cyclase activity. Salmeterol (100 nM) maximally stimulated cAMP accumulation in enzyme dispersed bovine trachealis cells and this was entirely inhibited by propranolol, as expected for beta-adrenergic stimulation. However, the same concentration of salmeterol also antagonized carbachol inhibition of cAMP accumulation and altered binding of carbachol to muscarinic receptors. These effects of salmeterol were sensitive to washing of the cells and this was not consistent with a beta-2-adrenergic mechanism. The findings suggested that the maximal, beta-2-adrenergic stimulation of cAMP accumulation by salmeterol was accompanied by a non-beta-2-adrenergic interaction of salmeterol with muscarinic receptors that attenuated muscarinic inhibition of adenylyl cyclase.
Ethier
M F
MF
Pulmonary, Allergy and Critical Care Medicine, University of Massachusetts Medical School, Worcester 01655, USA. Michael.Ethier@umassmed.edu
Dextradeur
T
T
Schaefer
O P
OP
Madison
J M
JM
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology; D007700:Kinetics; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000502:physiology; D000068299:Salmeterol Xinafoate; D014132:Trachea / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D000067956:Adenylyl Cyclase Inhibitors; D000318:Adrenergic beta-Agonists; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D000068299:Salmeterol Xinafoate; D011433:Propranolol; D000242:Cyclic AMP; D015232:Dinoprostone; D000420:Albuterol; D015056:1-Methyl-3-isobutylxanthine