ABSTRACT
Purinergic P2X receptors associated with the parasympathetic nerves supplying human bladder smooth muscle (detrusor) are implicated in control of detrusor contractility. The relative abundance of all seven subtypes colocalised with synaptic vesicles on parasympathetic nerves was examined in specimens from normal adult bladder and in adults with the urodynamics findings of sensory urgency (SU) to determine how receptor distribution varied in patients with a small bladder capacity. Alteration in control of detrusor innervation was examined with P2X subtype-specific antibodies and an antibody (SV2) against synaptic vesicles, using immunofluorescence and confocal microscopy. Detrusor samples were taken from: controls, at cystectomy for cancer or cystoscopic biopsy for haematuria (n=22, age 33-88 years) and adults with sensory urgency at cystoscopy/cystodistension (n=11, age 37-70 years). Normal adult specimens contained detrusor muscle innervated by parasympathetic nerves possessing large varicosities (1.2 microm) distributed along their length. These mostly all showed colocalised patches of presynaptic P2X(1,2,3,5) subtypes while presynaptic subtypes P2X(4,6,7) were present in only 6-18% of varicosities. Detrusor nerve varicosities from SU patients revealed general loss of all presynaptic P2X subtypes with the proportion containing receptors reducing to only 0.5-5% depending on P2X subtype. The same loss was recorded from the sensory nerves in the surrounding lamina propria. This specific loss of P2X receptors may impair control of detrusor distension and contribute to the pathophysiology of sensory urgency.
Subject(s)
Muscle, Smooth/innervation , Receptors, Purinergic P2/deficiency , Sensory Receptor Cells/metabolism , Urinary Bladder/innervation , Urinary Incontinence/metabolism , Adult , Aged , Aged, 80 and over , Epithelium/innervation , Epithelium/physiopathology , Female , Gene Dosage , Humans , Immunohistochemistry , Male , Middle Aged , Muscle, Smooth/pathology , Muscle, Smooth/physiopathology , Parasympathetic Fibers, Postganglionic/cytology , Parasympathetic Fibers, Postganglionic/metabolism , Receptors, Purinergic P2/genetics , Receptors, Purinergic P2X , Reference Values , Sensory Receptor Cells/pathology , Sensory Thresholds/physiology , Synaptic Vesicles/metabolism , Synaptic Vesicles/ultrastructure , Urinary Bladder/physiopathology , Urinary Incontinence/physiopathologyABSTRACT
Expression levels of the purinergic P2X receptor subunits (P2X(1) to P2X(7)) and P2Y(2) were examined in the endothelial cell layer of internal mammary artery (Ann. Thorac. Surg. 54 (1992) 652), radial artery (Ann. Thorac. Surg. 16 (1973) 111) and saphenous vein (Ann. Thorac. Surg. 20 (1975) 628) samples obtained at surgery for coronary artery bypass grafts using immunohistochemistry and confocal microscopy. Similar levels of P2X(1), P2X(2), P2X(3), P2X(7) and P2Y(2) were found in the endothelial cells in all vessels examined while the levels of P2X(5) and P2X(6) were uniformly lower. A clear difference was measured in P2X(4) expression between arteries and veins. Both radial and internal mammary arteries exhibited very low levels of P2X(4) whereas the level in the saphenous vein was 14.6 fold higher (P<0.0001), approaching that of the major receptor subtypes. These data showing strong expression of P2X(4) in veins have implications for the choice of vessels used in coronary artery bypass grafts given that P2X(4) is involved in calcium influx into endothelial cells, modulates blood vessel contractility and is up-regulated in situations involving intima proliferation suggesting vein grafts are more susceptible to developing atherosclerosis.
