Pertussis toxin-sensitive airway beta-adrenergic dysfunction by somatostatin.
To elucidate the effect of somatostatin and its mechanism of action on airway beta-adrenergic function, we studied canine bronchial smooth muscle under isometric conditions in vitro. Somatostatin (10(-6) M) inhibited the salbutamol-induced relaxation, so that the salbutamol concentration-response curves were displaced to higher concentrations (P < 0.01). This inhibition was dose dependent, the concentration of somatostatin required to produce a half-maximal effect being 10(-8) M. The relaxant responses to forskolin were likewise inhibited by somatostatin, but those to dibutyryl 3',5'--adenosine cyclic monophosphate (DB-cAMP), verapamil and nitroprusside were not. Somatostatin inhibited the salbutamol-induced accumulation of intracellular cAMP. These effects were abolished by the somatostatin antagonist cyclo [7-aminoheptanoyl-Phe-D-Trp-Lys-Thr (Bz)] or pertussis toxin. These observations suggest that somatostatin down-regulates beta-adrenergic function of airway smooth muscle through activation of an inhibitory guanine nucleotide (GTP)-binding regulatory protein, Gi, coupled to adenylate cyclase.
Tamaoki
J
J
First Department of Medicine, Tokyo Women's Medical College, Japan.
Tagaya
E
E
Yamauchi
F
F
Chiyotani
A
A
Konno
K
K
D037361:Adenylate Cyclase Toxin; D000595:Amino Acid Sequence; D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D004285:Dogs; D019204:GTP-Binding Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D037342:Pertussis Toxin; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors; D012132:Respiratory Muscles / Q000187:drug effects / Q000502:physiology; D013004:Somatostatin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000633:toxicity
D037361:Adenylate Cyclase Toxin; D011943:Receptors, Adrenergic, beta; D017481:Receptors, Somatostatin; D010566:Virulence Factors, Bordetella; C036876:cyclo(7-aminoheptanoyl-phenylalanyl-tryptophyl-lysyl-threonyl); D013004:Somatostatin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins