Direct evidence against a role of ATP as the nonadrenergic, noncholinergic inhibitory neurotransmitter in guinea pig tenia coli

Abstract

Electrical field stimulation of the isolated guinea pig tenia coli in the presence of a muscarinic receptor antagonist (atropine) and an adrenergic neuron blocker (guanethidine) produces relaxation. A large amount of indirect evidence has suggested that the neurotransmitter that is released from these nonadrenergic, noncholinergic inhibitory neurons is ATP or a related nucleotide, and the nerves have been termed "purinergic." A photoaffinity analog of ATP, arylazido aminopropionyl ATP, which produces a specific pharmacological antagonism of P2 purinergic receptors in isolated guinea pig vas deferens and urinary bladder, was utilized in the present study to evaluate directly whether ATP is the nonadrenergic, noncholinergic inhibitory neurotransmitter in tenia coli. By blocking postjunctional P2 receptors, arylazido aminopropionyl ATP produced a pronounced antagonism of relaxations induced by exogenously added ATP. Responses produced by ADP, AMP, and adenosine also were antagonized by arylazido aminopropionyl ATP, but to a lesser extent. Inhibitory responses to isoproterenol were not antagonized. Under these conditions of established, specific P2-receptor blockade of responses to exogenously added ATP, relaxations induced by field stimulation of intrinsic inhibitory nerves in the presence of atropine (1 microM) and guanethidine (1 microM) were not antagonized. Though these results provide no indication of the actual substance involved, they suggest strongly that the nonadrenergic, noncholinergic inhibitory neurotransmitter in the guinea pig tenia coli is not ATP.