Purinergic modulation of spontaneous activity and of responses to high potassium and acetylcholine in rat ileal smooth muscle.
1. In rat ileal smooth muscle both adenosine and ATP at 10(-4) M significantly enhanced spontaneous mechanical activity. The excitatory actions of adenosine were blocked by the P1 receptor antagonist 8-phenyltheophylline and the excitatory effects of ATP were significantly reduced by the P2 receptor antagonist quinidine. 2. The P2 receptor desensitizer alpha,beta-methylene-ATP was without effect on ACh responses nor did the stable analogue beta,gamma-methylene-ATP exert any effect on spontaneous mechanical activity. 3. Pretreatment with adenosine caused a dose-dependent enhancement of K-induced contractures in the ileum. Low adenosine concentrations slightly inhibited and high concentrations slightly enhanced ACh-induced contractures in the ileum. 4. ATP potentiated the phasic component of the ileal K-induced contracture but strongly inhibited tonic force at high concentrations. This agent slightly inhibited the phasic component of the ACh-induced contracture while strongly inhibiting ACh-induced tonic force. 5. alpha,beta-methylene-ATP inhibited ileal muscle ACh induced contractures while it potentiated both phasic and tonic K-induced contractures. beta,gamma-methylene ATP inhibited ACh-induced contractures but it enhanced K-induced phasic contractures while inhibiting K-induced tonic force. 6. The results of this study suggest that rat ileum may contain the A1 subtype of the P1 receptor but the evidence for a P2 receptor subtype is conflicting despite the inhibition of ATP actions by quinidine. 7. The inhibition of K- and ACh-induced tonic force suggests that adenosine and ATP interactions with ileal smooth muscle may inactivate slow voltage-dependent calcium channels leading to EC uncoupling.
Mahmod
S M
SM
Division of Biological Sciences, Institute of Environmental and Biological Sciences, Lancaster University, U.K.
Huddart
H
H
D000109:Acetylcholine / Q000494:pharmacology*; D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D007082:Ileum / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011983:Receptors, Purinergic / Q000187:drug effects*
D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate; D000241:Adenosine; D000109:Acetylcholine; D011188:Potassium