1 The a,-adrenoceptor subtypes mediating contractions of the smooth muscle in human prostatic urethra and branches of internal iliac artery were characterized in isometric contraction experiments. 2 Phenylephrine produced concentration-dependent contractions in both the urethra and artery. These responses were competitively inhibited by prazosin, WB4101 and 5-methyl-urapidil, and the slopes of Schild plots for all these antagonists were close to unity. 3 The pA2 values for prazosin were not significantly different between the urethra (9.42 ± 0.11; mean ± s.d.) and artery (9.50 0.27), while the pA2 values for WB4101 and 5-methyl-urapidil in the human prostatic urethra (8.94 0.19 and 8.42 0.14, respectively) were significantly greater than in the branches of human internal iliac artery (7.94 0.21 and 7.43 ± 0.22, respectively; P<0.01).4 Pretreatment with chlorethylclonidine (CEC) at concentrations ranging from 0.1 IJM to 1I00 1M attenuated the maximum contraction to phenylephrine in a concentration-dependent manner in both the urethra and artery. However, the urethra was significantly less affected by CEC than the artery. The pD'2 values (negative logarithm of the molar concentration of antagonist which reduced the maximum contraction to one half) in the urethra and artery were 4.35 ± 0.27 and 5.20 ± 0.37, respectively (P<0.0 1). 5 The present results indicate that there are distinct populations of a,-adrenoceptor subtypes in the human prostatic urethra and branches of the internal iliac artery. The a1-adrenoceptors responsible for the contraction of the human internal iliac artery branches are predominantly ax1-subtype, whereas those in the human prostatic urethra are considered to be not a,3, but atc or possibly O1A or a1A/D-subtype.
The distribution of calcitonin gene-related peptide-immunoreactive nerve fibers in the renal pelvis and ureter was examined by immunohistochemistry using whole-mount preparations and cryostat sections. The patterns of innervation were contrasted between the pelvis and ureter; the immunoreactive nerve fibers in the pelvis ran parallel to the long axis of each of the circular and longitudinal muscle layers, causing a lattice-like appearance of the nerve fibers. In the ureter, the immunoreactive fibers were accumulated in the subepithelial region and the longitudinal muscle. In both the pelvis and ureter, a portion of the nerve fibers of smaller caliber showed a swollen or beaded structure; they were located in the musculature and beneath the epithelium extending for considerable distances. Ligation of the ureter caused a marked decrease in the immunoreactive nerves in the pelvis and the proximal portion of the ureter, suggesting that the axonal flow in the calcitonin gene-related peptide-containing neurons of the ureter runs towards the pelvis.
Summary. To visualize the entire shape of the intraepithelial nerve fibers, whole mount preparations of the dog urethra were produced and immunostained with an antiserum against CGRP, one of the predominant substances contained in the nerves.The immunoreactive nerves in the lamina propria were smooth (non-beaded) in appearance and weak in immunoreaction. Within the epithelium, they displayed typical beaded profiles and were intense in immunoreaction. The intraepithelial fibers branched and wound into an extensive network with wide meshes ("reticular terminal"). The bead-like swellings included large ones resembling Herring bodies in hypophyseal neurosecretory fibers.Another type of nerve terminal, consisting of fine and weakly immunopositive fibers, was also found in the epithelium. These branched in dendritic or in dense bouquetlike fashion, occupying smaller areas ("bouquet-like terminals). Vesicular swellings often characterized these terminals, though they were smaller and more uniform in size and far less in their amount of immunoreactive substance than were the swellings in the reticular terminals. Both types of nerve terminals originated from the same nerve trunk.The connection between the reticular and bouquetlike terminals, which may presumably represent secretory and receptive parts, respectively, morphologically supports the possible occurrence of an axon reflex in the urethral CGRP neurons.Our whole mount preparations, when doubly stained with CGRP and serotonin antibodies, further revealed the CGRP-positive reticular terminals being closely associated with serotonin-or CGRP-immunoreactive paraneurons dispersed in the epithelium.
The aim of this study was to characterize endothelin receptor subtypes of the detrusor muscle of the human urinary bladder. The receptor subtypes mediating endothelin (ET)-1-induced activity in the human detrusor smooth muscles have been characterized using isometric contraction and reverse transcription–polymerase chain reaction (RT–PCR). ET-1 (a non-selective ET receptor agonist; 10-10 M to 10-6 M) exhibited concentration-dependent contractions in human urinary bladder with a plateau at concentrations above 3×10-7 M. Neither IRL1620 nor sarafotoxin S6c (both ETB-selective agonists; 10-10 M to 10-6 M) elicited contractile activity in the human urinary bladder detrusor smooth muscle. FR139317 (an ETA-selective antagonist; 10-7 M to 10-5 M) produced a marked shift to the right of the ET-1 concentration–response curve in human urinary bladder detrusor smooth muscle (from the Schild plot TpA2 = 7.96; slope = 0.95). In contrast, RES701-1 (an ETB-selective antagonist; 10-7 M to 10-5 M) had no effect on the ET-1 concentration–response curve. RT–PCR revealed positive amplification of ETA receptor mRNA fragment, but not ETB. These results indicate that the ET-1-induced contractile effects of urinary bladder detrusor smooth muscle seem to be mediated mainly by the ETA receptor, not by the ETB receptor.
The harmonic scalpel is useful for obtaining a clear parenchymal stump and hemostasis during nephron sparing surgery, although complete hemostasis of the arcuate or larger vessels cannot be achieved.
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