In vitro effects of bladder mucosa and an enkephalinase inhibitor on tachykinin induced contractility of the dog bladder.
Tachykinin-induced contractility of smooth muscle strips from dog bladders was studied in vitro, and the presence of substance P-like immunoreactivity and neurokinin A and neurokinin B-like immunoreactivity was examined in bladder sections. Nerve fibers with substance P-like immunoreactivity were present in the mucosa, submucosa and smooth muscle. Fibers were also found in nerves, intramural ganglia, and around blood vessels. Neurokinin A-like immunoreactivity had similar distribution, and no neurokinin B-like immunoreactivity was observed. Removal of the mucosa significantly enhanced the sensitivity and the maximum responses to the tachykinins. After removing the mucosa, the sensitivity to these tachykinins increased 0.4 to 0.5 log units (p less than 0.02). The responses to carbachol were not altered by mucosa removal. The leftward shifts of the concentration-response curves for neurokinin A were of similar magnitude after removal of the mucosa, and after pretreatment with phosphoramidon (10 microM), an enkephalinase inhibitor, in the presence of mucosa. However, phosphoramidon did not alter the sensitivity of the bladder strips to neurokinin B, and slightly changed the sensitivity to substance P (0.2 log units). Additional shifts of the substance P and neurokinin A curves to the left were observed in the presence of phosphoramidon when the mucosa was removed (0.6 and 0.5 log units, p less than 0.005). The order of potency for the tachykinins (neurokinin A greater than substance P) was not altered by mucosa removal, addition of phosphoramidon, or both. Neurokinin A was degraded by enkephalinase located in the bladder mucosa and addition of phosphoramidon or mucosa removal resulted in an inhibition or loss of enkephalinase activity. It is concluded that the responses to neurokinin A, which acts on NK-2 type of receptors, prevail on the dog bladder.
Saban
R
R
Department of Surgery, School of Veterinary Medicine, University of Wisconsin-Madison 53706.
Keith
I M
IM
Nielsen
K T
KT
Christensen
M M
MM
Rhodes
P R
PR
Bruskewitz
R C
RC
D000818:Animals; D004285:Dogs; D066298:In Vitro Techniques; D009092:Mucous Membrane / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D015320:Tachykinins / Q000502:physiology*; D001743:Urinary Bladder / Q000502:physiology*
D015320:Tachykinins; D015260:Neprilysin