The Atropine‐resistance of the Response to Intrinsic Nerve Stimulation of the Guinea‐pig Bladder

Abstract

The urinary bladder responds to parasympathetic nerve stimulation by contraction but it has been shown in several species that this response is not blocked by atropine. Acetylcholine applied to isolated bladder preparations, on the other hand, produces a contraction which is abolished by atropine in the manner characteristic of a muscarinic response.As early as 1911, Langley observed this anomalous behaviour of the bladder in the dog, cat and rabbit but until recently studies of this phenomenon in other species have been few. Burnstock & Campbell (1963) and Burnstock, O'Shea & Wood (1963) have described its occurrence in the ring-tailed possum (Pseudocheirusperegrinus) and the toad (Bufo marinus). Carpenter (1963) also noted the same results for the bladder of the rat.This paper describes studies on the response of the isolated bladder of the guinea-pig to electrical stimulation and to application of drugs. METHODSAdult guinea-pigs of either sex, weighing 250 to 400 g, were killed by a blow on the head. Both ureters were tied and cut and the bladder was flushed out with 1 to 2 ml. of Locke solution through a cut in the urethra. A glass cannula was then inserted into the bladder through the urethra, tied into place and filled with Locke solution to distend the bladder. The cannulated bladder was immersed in the organ-bath (25 ml. capacity) filled with Locke solution and bubbled with 95%. oxygen and 5% carbon dioxide. The cannula was connected to a U-tube containing black ink and the intraluminal pressure under these conditions was 60 to 80 mm of water. One arm of the U-tube passed through a close-fitting sleeve in which length-wise slits had been cut on opposite sides. The sleeve was illuminated by a lamp and the light passing through the slit was allowed to fall on a selenium photoelectric cell. Movement of the bladder displaced the fluid in the cannula, varying the level of the ink of the U-tube and so changing the illumination of the photo-cell. The potential changes so produced were recorded directly on a self-balancing potentiometric recorder. For electrical stimulation one platinum electrode was inserted through the cannula into the lumen of the bladder and another, which was made the anode, was placed directly in the organ-bath. The shocks were rectangular, submaximal (2 to 5 V) or supramaximal (20 V), and of 0.5 to 1 msec duration. The stimulus frequency was varied. The preparation showed considerable spontaneous activity, although this could be reduced by keeping the bath temperature at 300 C.Treatment ofguinea-pigs with reserpine. Reserpine was dissolved in a 20% solution of ascorbic acid and a dose of 10 mg/kg was given intraperitoneally on four successive days, the animal being used on the fifth day. During this treatment the animals were kept in a warm room.

Atropine and Micturition Responses by Rats With Intact and Partially Innervated Bladder

“…While the effects of these drugs on nerve-induced bladder contractions have been studied extensively in vivo and in vitro, (Edge, 1855;Ursillo & Clark, 1956;Carpenter, 1963;Hukovic, Rand & Vanov, 1965;Chesher & Thorp, 1965;Downie & Dean, 1977) their effect on micturition by unrestrained animals have not. The reflex control of the urinary bladder depends on several autonomic pathways.…”

Atropine Resistance and Muscarinic Receptors in the Rat Urinary Bladder

“…There is strong evidence that acetylcholine is a transmitter in the rat urinary bladder: (1) nerveinduced responses of the bladder are potentiated by physostigmine (Ursillo & Clark, 1956;Carpenter, 1963;Chesler & Thorp, 1965;Hukovic, Rand & Vanov, 1965) (2) acetylcholine accumulates in the bathing solution in vitro in proportion to the stimulus rate (Carpenter & Rand, 1965;Chesler, 1967); (3) the responses of the rat bladder and the release of acetylcholine during stimulation are greatly reduced following pretreatment of the rats with Cl. botulinum toxin (Carpenter, 1967).…”

DMPP-induced relaxation of the guinea pig urinary bladder.

“…The contractions elicited by transmural stimulations with short pulses of 0.5 msec duration are believed to be due to the stimulation of nerves and not to that of the muscle (Chesher and Thorp 1965;Burnstock et al 1972). In this case, cholinergic nerves play a major role, even though a problem of atropine-resistant nerve element remains (Taira 1972;Carpenter 1977).…”