Physiology and Pharmacology of the Human Ureter: Basis for Current and Future Treatments

Abstract

Introduction: This article sets out to be a review regarding agents that affect contraction and relaxation of the ureter in order to establish a basis for current and future treatments for upper urinary tract obstruction. Material and Methods: A complete review of the English literature using MEDLINE was performed between 1960 and 2007 on ureter physiology and pharmacology with special emphasis on signal transduction mechanisms involved in the contractile regulation of the human ureter. Results: Activation of muscarinic and adrenergic receptors increases the amplitude of ureteral contractions. The sympathetic nerves modulate the contractions by α-adrenoceptors and relaxation by β-adrenoceptors. The purinergic system is important in sensory/motor functions and ATP is an important non-adrenergic non-cholinergic (NANC) agent causing contraction. Nitric oxide (NO) is a major inhibitory NANC neurotransmitter causing relaxation. Serotonin causes contraction. Prostaglandin-F₂α contracts whereas prostaglandin-E₁/E₂ relaxes the ureter. Phosphodiesterases (PDE) and the Rho-kinase pathway have recently been identified in the human ureter. PDE-IV inhibitors, K⁺ channel openers, calcium antagonists, α₁-adrenoceptor antagonists and NO donors seem to be promising drugs in relieving obstruction and facilitating stone passage. Conclusions: Further understanding of the ureteral function and pharmacology may lead to the discovery of promising new drugs that could be useful in relieving ureteral colic, facilitating spontaneous stone passage, preparing the ureter for ureteroscopy as well as acting adjunctive to extracorporeal shock-wave lithotripsy.

Purinergic signalling in the urinary tract in health and disease

“…This is similar to the uroteric pressure threshold for pain measured by Risholm [576]. In a review of the physiology and pharmacology of the human ureter, it was suggested that purinergic receptors might be target analgesics for the treatment of ureteral colicky pain and that an additional advantage might be facilitating spontaneous ureteral stone passage [128].…”

498 Does Diabetes Affect Distribution and Number of Interstitial Cells and Neuronal Tissue in the Ureter, Bladder, Prostate and Urethra of Humans?

“…It is known that pacemaker cells located in the renal pelvis initiate spontaneous peristaltic activity [19,20,21]. Electrical activity in the ureter is propagated to the distal parts as a contraction wave propelling urine in boluses distally from the renal pelvis into the urinary bladder [21,22]. In our study, c-kit positive ICs were demonstrated in the lower ureter in both groups, suggesting a possible role in ureteric peristalsis.…”

“…The number of nerves was also similar along the whole urinary tracts of both groups. It is known that pacemaker cells located in the renal pelvis initiate spontaneous peristaltic activity [19,20,21]. Electrical activity in the ureter is propagated to the distal parts as a contraction wave propelling urine in boluses distally from the renal pelvis into the urinary bladder [21,22].…”

Cell Biology of Ureter Development

“…62 The mature ureter also contains adrenergic, cholinergic, nitrergic, and sensory nerves, the activities of which modify its contractility. 63 A theoretical scheme, in which the onset of fetal urine production by the kidney enhances ureteric SM differentiation and function, is depicted in Figure 3.…”