Desensitization of the guinea‐pig urinary bladder by the enantiomers of adenylyl 5′‐(β,γ‐methylene)‐diphosphonate and by substance P

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Abstract
Adenosine 5′‐triphosphate (ATP), substance P (SP) and non‐cholinergic nerve stimulation contracted the guinea‐pig urinary bladder. SP and two poorly‐degradable analogues of ATP, the enantiomers of adenylyl 5′‐(β,γ‐methylene)‐diphosphonate (AMP‐PCP and L‐AMP‐PCP), were used to desensitize the guinea‐pig bladder. Desensitization of the bladder by AMP‐PCP (50 μM) or by L‐AMP‐PCP (50 μM) abolished the responses to ATP, and inhibited the responses to non‐cholinergic nerve stimulation and to SP. The responses to histamine were unaffected. Desensitization by SP (1 μM) inhibited the responses to SP itself, but not the responses to ATP, L‐AMP‐PCP or non‐cholinergic nerve stimulation. These results suggest that SP may act partly by releasing ATP, and support the suggestion that ATP rather than SP is the non‐cholinergic stimulatory transmitter.