POTENTIATION OF PURINERGIC NEUROTRANSMISSION IN GUINEA-PIG URINARY-BLADDER BY HISTAMINE

Patients suffering from the inflammatory condition of interstitial cys titis frequently exhibit an increased number of mast cells in the blad der. To determine whether mast cell mediators have the potential to in fluence the neurogenic contraction of the bladder smooth muscle and th ereby possibly contribute to the symptoms of interstitial cystitis, we examined the effects of histamine, a major inflammatory mediator of m ast cell origin, on nerve- and agonist-induced contractions of in vitr o strips of guinea pig urinary bladder. Histamine (10 mu M.) potentiat ed by more than 50% the nerve-induced contraction of bladder strips ev oked by field stimulation with 0.5 msec. pulses at 4 Hz. Because the n eurogenic contraction of the bladder is mediated by at least two neuro transmitters, acetylcholine (ACh) and ATP, we examined the effects of histamine on each of these transmitters. Histamine potentiated respons es to the purinergic component of the neurogenic response (that part o f the neurogenic response that remains after treatment with atropine) and potentiated responses to exogenously applied ATP. Histamine did no t potentiate the response to the cholinergic component of the neurogen ic response (that part of the neurogenic response that remains after d esensitization of purinoceptors with alpha, beta-methylene ATP) nor re sponses to carbachol, a cholinergic agonist. These results indicate th at histamine potentiates the neurogenic response of the bladder by inf luencing the purinergic component, apparently at postjunctional sites.