POTENTIATION BY BRADYKININ AND SUBSTANCE-P OF PURINERGIC NEUROTRANSMISSION IN URINARY-BLADDER

Purpose: The higher than normal levels of substance P (SP) and the kin ins in patients suffering from interstitial cystitis suggest that they may contribute to the complex symptoms of the condition. The purpose of our experiments was to determine whether SP and bradykinin (BK) inf luence the excitatory motor innervation of the urinary bladder. Materi als and Methods: Strips of guinea pig urinary bladder were placed in i solated tissue baths, and the influence of SP and BK on contractions i nduced by transmural electrical stimulation and cholinergic and purine rgic agonists was evaluated. Results: Substance P and BK potentiated r esponses to the purinergic component of the neurogenic stimulation (th at part of the contractile response that remains after treatment with atropine) and potentiated responses to exogenously applied adenosine t riphosphate (ATP). The peptides did not potentiate the response to the cholinergic component of the nerve-induced contraction (that part of the neurogenic response that remains after desensitization of purinoce ptors with alpha,beta-methylene ATP) nor responses to carbachol. The p otentiating actions of SP and BK were reduced but not abolished by tre atment with meclofenamic acid. Conclusions: Substance P and BK potenti ate the neurogenic response of the bladder by influencing the purinerg ic component of the excitatory motor innervation, apparently at a post junctional site. Prostaglandins may be involved in mediating some of t he actions of these peptides.