High affinity binding sites for [3H]substance P in urinary bladders of cats with interstitial cystitis.
OBJECTIVE
Pain is a common feature of interstitial cystitis (IC). Although the effects of IC on sensory neuron density have been investigated, its influence on substance P receptor (SPR) numbers and function are not well known. To evaluate the role of SPR in cats with IC, we measured the affinity (Kd), numbers (Bmax), and substrate specificity of binding sites for [3H]SP in urinary bladders of healthy cats and cats suffering from IC.


METHODS
Radioligand binding assays of cat and rat brain, normal cat bladders, and inflamed bladders from cats diagnosed with IC were conducted using [3H]SP to determine SPR affinity and numbers. Binding sites for [125I]SP were identified using autoradiography in slide-mounted frozen tissue sections, and their specificity determined with competition binding studies.


RESULTS
In bladder homogenate binding studies, low affinity SP binding sites for [3H]SP were found both in normal and inflamed tissue, whereas high affinity binding sites were found in inflamed bladder tissue only. Based on autoradiographic studies, high affinity binding appeared to be to small blood vessels, and to be specific for substance P, a pharmacology consistent with the neurokinin-1 receptor (NK1R).


CONCLUSIONS
Upregulation of NK1R may be part of the pathophysiology of IC, as it is in some other inflammatory diseases. If so, more specifically targeted therapies for IC may become available.
Buffington
C A
CA
Department of Veterinary Clinical Sciences, The Ohio State University, Columbus, USA.
Wolfe
S A
SA
D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001667:Binding, Competitive; D001808:Blood Vessels / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002415:Cats; D018856:Cystitis, Interstitial / Q000378:metabolism* / Q000473:pathology; D005260:Female; D007457:Iodine Radioisotopes; D008297:Male; D015288:Neurokinin A / Q000378:metabolism; D015287:Neurokinin B / Q000378:metabolism; D010146:Pain / Q000378:metabolism; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000032:analysis / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism* / Q000502:physiology; D013379:Substrate Specificity; D014316:Tritium; D015854:Up-Regulation; D001743:Urinary Bladder / Q000378:metabolism* / Q000473:pathology
D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D018040:Receptors, Neurokinin-1; D014316:Tritium; D013373:Substance P; D015288:Neurokinin A; D015287:Neurokinin B