Pertussis toxin-sensitive muscarinic relaxation in the rat iris dilator muscle.
1. The effects of pertussis toxin (PTX) on contraction and/or relaxation induced by agonists or transmural nerve stimulation (TNS) were examined in the rat iris dilator and sphincter muscles. 2. TNS in the presence of phentolamine induced an atropine-sensitive biphasic response: initial contraction followed by relaxation in dilator muscles. Exogenously applied acetylcholine (ACh) elicited a large relaxation at low doses (3 microM or less) and a concentration at high doses. 3. Only the ACh-induced relaxation was affected by injection of PTX (10 ng) into the anterior eye chamber. Relaxation was decreased 12 h after injection and had completely disappeared after 24 h. Relaxation recovered in part 3 weeks and almost completely 8 weeks after PTX treatment. A gradual decrease in muscarinic relaxation in a dilator muscle was also observed in vitro after addition of PTX to the bathing solution. 4. The pA2 values of muscarinic blockers, pirenzepine, AF-DX 116, 4-DAMP, and himbacine for competitive antagonism to ACh-induced contraction were 7.14, 6.53, 9.03, and 6.80, respectively, in PTX-pretreated dilator muscles. These values are comparable to those obtained in parasympathectomized dilator muscles and may indicate involvement of M3 or M3-like receptors in muscle contraction. 5. Pretreatment with PTX did not significantly affect contraction induced by noradrenaline or 5-hydroxytryptamine or the relaxation induced by isoprenaline in dilator muscles. 6. In conclusion, among several agonist-induced responses in the rat iris dilator and sphincter muscles, only muscarinic relaxation in dilator muscle occurs via activation of PTX-sensitive GTP binding proteins.
Yamahara
N S
NS
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
Tanaka
M
M
Imaizumi
Y
Y
Watanabe
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003959:Diamines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005663:Furans; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007498:Iris / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008845:Microinjections; D018727:Muscarinic Antagonists; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009281:Naphthalenes; D010276:Parasympatholytics / Q000494:pharmacology*; D037342:Pertussis Toxin; D010646:Phentolamine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000008:administration & dosage / Q000494:pharmacology*
D000470:Alkaloids; D003959:Diamines; D005663:Furans; D018727:Muscarinic Antagonists; D009281:Naphthalenes; D010276:Parasympatholytics; D010880:Piperidines; D011976:Receptors, Muscarinic; D010566:Virulence Factors, Bordetella; D010890:Pirenzepine; D001285:Atropine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; C048172:himbacine; D000109:Acetylcholine; C054938:methoctramine; C048593:otenzepad; D010646:Phentolamine