NONCHOLINERGIC NEUROTRANSMISSION AND THE EFFECTS OF PEPTIDES ON THE URINARY-BLADDER OF GUINEA-PIGS AND RABBITS

Supramaximal repetitive field stimulation with pulses of 50 .mu.s produced contraction of strips of bladder from rabbits and guinea-pigs. Atropine reduced responses at all frequencies to about 60% and the contraction was poorly maintained. With the double sucrose-gap technique large excitatory junction potentials (e.j.p.s) were recorded with superimposed action potentials. These were not reduced by atropine or phentolamine. Substance P (SP) produced contraction and increased the frequency of spontaneous action potentials recorded with micro-electrodes from bladder strips. Vasoactive intestinal peptide (VIP) produced relaxation and slowed action potentials in rabbit but had no effect on guinea-pig; neurotensin, somatostatin and leu-enkephalin were without action in either species. When the tissue was kept in contact with SP, a second application after 10 min produced only a small contraction suggesting that SP receptors were densensitized. However, the electrical response to field stimulation was unchanged and the mechanical response was increased. Chymotrypsin reduced mechanical responses to SP but had no effect on responses to field stimulation. The SP analogue, D-Pro2, D-Phe7, D-Trp9-SP, had no effect on responses to SP or to field stimulation. It is concluded that the bladder receives excitatory non-cholinergic innervation which is responsible for a large excitatory junction potential and contraction. Although SP can contract the detrusor muscle, it is unlikely that it is an excitatory transmitter or that any of the five peptides act as modulators of transmitter release.