Human female bladder and its noncholinergic contractile function

Abstract

The response of human female detrusor muscle to field stimulation at varying voltages, durations, and frequencies was studied in vitro. In addition, the effects of adrenergic and cholinergic agonists and antagonists, and various nerve toxins were studied. Beta-adrenergic receptors were found in detrusor muscle but no significant adrenergic innervation was seen; no alpha-adrenergic receptors were seen. Atropine, scorpion venom, tetrodotoxin, beta bungarotoxin and hemicholinium were found to inhibit bladder contraction at short-pulse durations and low frequencies by approximately 50%. Black widow spider venom was seen to abolish bladder contractions entirely. It is concluded that acetylcholine is the neurotransmitter responsible for approximately 50% of bladder contraction. The remaining 50% would seem to be noncholinergic and not dependent on fast sodium channels for transmission of excitation, but would seem to be due to a structure with a short-membrane time constant, such as nerve, and is sensitive to black widow spider venom.

Impairment of ATP hydrolysis decreases adenosine A1 receptor tonus favoring cholinergic nerve hyperactivity in the obstructed human urinary bladder

“…ATP was shown (1) to be a co-transmitter with acetylcholine (ACh) in the parasympathetic control of bladder contraction [30], (2) to activate sensory nerves during bladder filling conveying both normal and abnormal sensations like urgency and pain [31,32], and (3) to participate in the central control of bladder reflexes [33]. However, not so much is known about the effects of adenosine, the breakdown product of extracellular ATP metabolism.…”

“…Although it is generally accepted that acetylcholine (ACh) acting on smooth muscle muscarinic receptors is the primary effector controlling bladder emptying, neural stimulation of the bladder is only partially inhibited by atropine in many species, including humans [2,3]. In keeping with the purinergic hypothesis proposed by Burnstock, it is now accepted that ATP is responsible for the atropine-resistant component of parasympathetic contraction of the detrusor [4,5].…”

Pharmacology of the Lower Urinary Tract: Basis for Current and Future Treatments of Urinary Incontinence

“…The role of a NANC mechanism in the contractile activation of the human bladder is still disputed (Andersson, 1993;de Groat and Yoshimura, 2001). Cowan and Daniel (1983) found that acetylcholine was responsible for approximately 50% of the electrically induced contraction in strips of the normal human detrusor. In contrast, Sjögren et al (1982), who investigated morphologically normal detrusor samples from patients undergoing bladder surgery for various reasons, found that atropine caused more than 95% inhibition of electrically evoked contractions.…”

Effect of Alpha-Chymotrypsin on the Nonadrenergic, Noncholinergic Contraction of the Rat Urinary Bladder in vitro

“…The postganglionic nerve-evoked contrac tile response of the urinary bladder of most vertebrates including human is only partially blocked by antimuscarinic agents such as atropine and relatively unaffected by alphaand beta-adrenergic inhibitors or nicotonic antagonists [1][2][3][4], In the human female blad der such NANC neurotransmission has been estimated to be responsible for up to 50% of the contractile response [10]. The list of puta tive NANC neurotransmitters is long and in cludes purine nucleotides, 5-hydroxytryptamines, gamma aminobutyric acid, dopamine, peptides, and, more recently, nitric oxide [1,11].…”