Controlling mesenchymal stem cell differentiation by TGFΒ family members

Mesenchymal stem cells can differentiate into various tissue types including bone, cartilage, fat, and muscle. Transforming growth factor- (TGF) family members, including TGFs and bone morphogenetic proteins (BMPs), play important roles in directing fate decisions for mesenchymal stem cells. TGF can provide competence for early stages of chondroblastic and osteoblastic differentiation, but it inhibits myogenesis, adipogenesis, and late-stage osteoblast differentiation. BMPs also inhibit adipogenesis and myogenesis, but they strongly promote osteoblast differentiation. TGF family members signal via specific serine/threonine kinase receptors and their nuclear effectors, termed Smad proteins. In this review we discuss recent advances in our understanding of the molecular mechanisms by which TGF family members control mesenchymal stem cell differentiation.Presented at the 17th Annual Research Meeting of the Japanese Orthopaedic Association, Aomori, Japan, October 2002     

Quantitative ultrasound of bone and clodronate effects in thalassemia-induced osteoporosis

Osteoporosis in -thalassemia major has emerged as a topic of interest since optimized transfusion regimens have increased life expectancy and quality in these patients. Although the pathogenesis of thalassemic osteopathy is multifactorial, the evidence of an increased resorption phase suggests that the use of antiresorptive drugs such as bisphosphonates can be considered a valuable therapeutic strategy to reduce bone turnover and the risk of fragility fractures. We compared the effects of long-term cyclical clodronate therapy (300mg intravenous infusion every 3 weeks for 2 years) and of an active placebo (calcium 1 vitamin D) on bone mass and bone turnover in 30 male patients with -thalassemia major. We also tested the possibility of using quantitative ultrasound (QUS) for assessing bone involvement in thalassemic osteopenia and in monitoring the response to antiresorptive therapy. Broadband ultrasound attenuation (BUA) was significantly reduced in patients with -thalassemia major as compared to healthy controls. In calcium and vitamin D-treated patients, a significant decline in spine, femoral, and total body areal bone density was observed. In the patients given intravenous clodronate we measured a substantial stability of bone mass, which was not significantly changed at the end of the study. The urinary excretion of deoxypyridinoline (a marker of bone resorption) showed a progressive significant decline throughout the study period in clodronate-treated patients. No significant change was observed in BUA values in both groups of patients. These results indicate that intermittent intravenous clodronate administration was not able to increase areal bone density in our thalassemic patients. Moreover, this is the first study to have assessed the usefulness of broadband ultrasound measurements in -thalassemia major.     

Prediction of chronic renal allograft dysfunction from evaluations of TGFΒ1 and the renin-angiotensin system

Background. Growth factors, cytokines, and the renin-angiotensin system (RAS) are involved in chronic allograft dysfunction. However, it is unclear whether clinical evaluations of TGF1 and the RAS in longterm stable transplant patients can predict the development of chronic allograft dysfunction. Methods. Urinary TGF1 excretion and the response of plasma renin activity (PRA) to angiotensin I converting-enzyme inhibition (ACE-I) were prospectively examined in transplant patients who had had stable graft function (n = 16) for at least 1 year after renal transplantation. Four-year follow-up studies were undertaken to evaluate the impact of these parameters on the development of chronic allograft dysfunction. Results. Urinary TGF1 excretion and PRA response to ACE-I in renal transplant patients who developed chronic allograft nephropathy 4 years after the evaluations (n = 7) were significantly higher and greater, respectively, than these values in those who did not (n = 9; P 0.01). If the cutoff level for urinary TGF1 excretion was 250pg/min, the 4-year positive predictive value (PPV) with respect to the development of chronic allograft nephropathy was 83% and the negative predictive value (NPV) was 78% (sensitivity [sen.], 71%; specificity [sp.], 88%). If the cutoff level for PRA at 60min after ACE-I was 4.0ng/ml per h, the 4-year PPV was 71% and NPV was 75% (sen., 70%; sp., 75%). The stable transplant patients with high TGF1 excretion and exaggerated PRA response showed significantly higher rates of chronic allograft dysfunction than those with low TGF1 excretion and weak PRA response. Conclusions. This study demonstrates that some transplant patients with longterm stable graft function show increases in the activities of the TGF system and the RAS. Evaluations of urinary TGF1 excretion and PRA response to ACE-I present a possibility for predicting the development of chronic allograft dysfunction, with significant 4-year predictive values.     

Effect of hemodialysis and renal failure on serum biochemical markers of bone turnover

The aim of the present study was to evaluate the effect of hemodialysis and renal failure on serum bone markers. Serum total alkaline phosphatase (TAP), procollagen type I aminoterminal propeptide (PINP), and -carboxyterminal telopeptide of type I collagen (-CTX), as well as intact parathyroid hormone (iPTH), creatinine, and total protein were measured in 14 patients with endstage renal disease (ESRD) before and at 1, 2, and 4h during a hemodialysis session, and at the same sampling interval in 6 renal transplant recipients. The results were compared to those obtained in 20 healthy adults. All patients showed increased baseline mean values of PINP, -CTX, and iPTH. -CTX differed significantly between hemodialysis patients and renal transplant recipients. TAP and -CTX were the only markers which correlated with iPTH (P 0.05) and creatinine values (P 0.001), respectively. Renal transplant recipients did not show significant variations in the evolution of mean values of bone markers throughout the study, whereas, during the dialysis period, all the bone markers analyzed in the study showed a significant change. The change differed depending on the marker considered: -CTX showed a significant decrease at the end of the session, TAP increased at this time and, although PINP showed an initial increase during hemodialysis, no significant changes were observed at the end of the session. We conclude that bone markers are significantly influenced by hemodialysis, especially serum TAP and -CTX. ESRD is associated with an increase in these bone markers, in some cases related to iPTH values and in others to glomerular function. These findings should be taken into account when evaluating bone markers in these patients.     

Significance of serum CrossLaps as a predictor of changes in bone mineral density during estrogen replacement therapy; comparison with serum carboxyterminal telopeptide of type I collagen and urinary deoxypyridinoline

The newly developed Elecsys -CrossLaps/serum assay measures C-terminal telopeptide of type I collagen and has thus been proposed as a reliable serum marker for bone resorption. We investigated its usefulness for monitoring the therapeutic effect of estrogen replacement therapy on bone turnover and bone mineral density (BMD) in patients with postmenopausal osteoporosis. Serum -CTx decreased by 43.2% ± 9.2% (mean ± SD), and 55.1% ± 7.0% at 3 and 6 months, respectively, after initiation of estrogen replacement therapy (ERT), which was significantly greater than the respective value of urinary excretion of deoxypyridinoline (DPD) (27.8% ± 4.1%, 34.1% ± 4.9%, respectively) or pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) assay (14.5% ± 4.1%, 13.1% ± 5.0%, respectively). The percent reduction in serum -CTx at 1, 3, and 6 months after initiation of ERT was significantly correlated in a negative manner with the percent increase in spinal BMD at 6 months. Further, ROC analysis to determine the significance of the percent change in bone resorption markers after 3 months of ERT in predicting the gain in spine BMD after 6 months suggested that serum -CTx and urinary DPD might provide a more discriminating indicator than serum ICTP. In conclusion, the findings suggest that the Elecsys -CrossLaps/serum assay provides a sensitive, and thus useful, tool for assessing bone resorption state in Japanese patients.     

The effects of prolonged controlled hypotension induced by prostaglandin E1 on renal tubular function

The effects of the prolonged 3-hour and 6-hour controlled hypotension induced by prostaglandin E₁ (PGE₁) on renal tubular function have been comparatively studied with trimethaphan (TMP; 3-hour hypotensive anesthesia) and enflurane deep anesthesia (6-hour hypotensive anesthesia), using the urine N-acetyl--D-glucosaminidase (NAG index) and the serum and urine ₂-microglobulin (fractional clearance of ₂-m; Fc-₂-m) as markers. During 3-hour and 6-hour controlled hypotension PGE₁, NAG index and Fc-₂-m and urine volume could be maintained without remarkable changes. In the group with TPM, NAG index and Fc-₂-m significantly increased. The increasing trend was also noted over time in deep anesthesia with enflurane. On 1st postoperative day, Fc-₂-m significantly increased in PGE₁ group in both 3-hour and 6-hour hypotensive anesthesia, whereas it restored to normal on 2nd postoperative day. Also, in TMP and enflurane deep anesthesia, Fc-₂-m significantly increased on 1st postoperative day. With the latter, significant increase was also observed on 2nd postoperative day. These results suggest that, in 3-hour and 6-hour controlled hypotension induced by PGE₁, renal tubular function is normally maintained and that it is useful for prolonged controlled hypotensive anesthesia. However, further study is necessary because tubular dysfunction might appear on 1st postoperative day.(Fukusaki M, Shibata O, Fujigaki T et al.: The effects of prolonged controlled hypotension induced by prostaglandin E₁ on renal tubular function. J Anesth 4: 197–205, 1990)     

Hypokalemic rhabdomyolysis in a child with Bartter’s syndrome

Hypokalemia represents a rare cause of rhabdomyolysis. Some reports have described a few adult patients affected by Bartters syndrome and Gitelmans syndrome with rhabdomyolysis due to severe hypokalemia. We report the first pediatric patient with Bartters syndrome in whom rhabdomyolysis developed when her plasma potassium level was less than 2 mEq/l. Prompt intravenous fluid and potassium prevented tubular damage and acute renal failure. We recommend determining serum creatine phosphokinase in all patients affected by Bartters syndrome and profound hypokalemia.     

Identification of α1-adrenoceptor subtypes in the dog prostate

Summary The ₁-adrenoceptor subtypes of dog prostate were characterized in binding and functional experiments. In saturation experiments, [³H]prazosin bound to ₁-adrenoceptors with high affinity. In the displacement experiments, unlabelled prazosin and WB4101 biphasically inhibited the binding of 400 pM [³H]prazosin, suggesting the presence of at least two distinct affinity sites for prazosin or WB4101. The proportion of high-affinity sites was approximately 10%. HV723 also recognized two distinct affinity sites but the proportion of high-affinity sites was approximately 20%. From these results the presence of three distinct ₁-adrenoceptor subtypes was suggested: presumably subtypes _1A (high affinity for prazosin and WB4101), _1N (high affinity for only HV723) and _1L (low affinity for the three antagonists) according to the recently proposed ₁-adrenoceptor subclassification. The density of subtype _1L was much higher than that of subtypes _1A and _1N subtypes. In the functional experiments, prazosin, WB4101 and HV723 competitively antagonized the contractile response to noradrenaline with low affinities close to those estimated for the _1L subtypes. These results suggest that the contractile response to noradrenaline in the dog prostate is mediated predominantly through _1L subtype -adrenoceptors.     

Beneficial Effects of Apolipoprotein A-I on Endotoxemia

Purpose. Although many studies have shown the beneficial effects of lipoproteins on animals with endotoxemia, little is known about the impact of apolipoprotein A-I (apoA-I) on tumor necrosis factor (TNF-) release in response to lipopolysaccharide (LPS). The present study was conducted to determine whether the administration of apoA-I inhibits the release of TNF- and influences the survival rate of rats with endotoxemia.Methods. Forty male Wistar rats were divided randomly into four groups. Rats in the first and second groups were given 1mg/kg LPS intraperitoneally (i.p.) and blood was collected 1h later to measure the serum levels of TNF-. Either 10mg/kg apoA-I or Tris-buffered saline was injected i.p. and the serum TNF- levels were measured again 2h later. Rats in the third and fourth groups were given 5mg/kg LPS. Following the administration of 10mg/kg apoA-I or Tris-buffered saline, animals were observed for 5 days and survival rates were determined.Results. ApoA-I inhibited the release of serum TNF- and improved the survival rates of rats with endotoxemia.Conclusion. The administration of apoA-I suppressed the TNF- release in endotoxemia and decreased the mortality rates of rats.     

Expression of PDGF,PDGF-Receptor,EGF-Receptor and sex hormone receptors on meningioma

Summary The expression of platelet derived growth factors (PDGF), the PDGF-Receptor (R) ( and types), epidermal growth factor (EGF)-Receptor (R) and sex hormone (oestrogen and progesterone) receptors was studied in 22 meningiomas. All tumours were PDGF-R type positive and 21 (95%) were PDGF positive. Only 2 (9%) were PDGF-R type positive, 13 (59%) were EGF-R positive. The expression of these proteins was not related to the histological type or the malignancy of the meningiomas although the expression of PDGF and PDGF-R tended to be stronger in malignant meningiomas.Oestrogen and progesterone receptor protein were examined in 19 patients (10 females and 9 males). None of the meningioma cells revealed oestrogen receptor protein while 17 (89%) of the 19 meningiomas were positive for progestrone receptor protein. The expression of progesterone receptor was not related to histological type or malignancy.Our studies suggest that the autocrine system, through PDGF and PDGF-R type , may play an important role in the tumourigenicity of meningiomas. EGF-R was present in almost half and progesterone receptor in most of the meningiomas. There was no correlation between the expression of either PDGF, PDGF-R or EGF-R and the expression of progesterone receptor protein.     

A systematic review of the management of hangman’s fractures

During the past 30 years various treatment protocols for hangmans fractures have been attempted. In order to guide the management of hangmans fractures, different classifications have been introduced. However, opinions on operative or nonoperative treatment have not yet been solidified. To evaluate both conservative and operative management of hangmans fractures in the published literature and to provide appropriate guidelines for treatment of hangmans fractures, a systematic review of the literature regarding the management of hangmans fractures was performed. An English literature search from January 1966 to January 2004 was completed with reference to treatment of hangmans fractures. The classification for treatment guidance from the literature was also reviewed. Regarding a primary therapy for hangmans fractures, there were 20 papers (62.5%) that advocated for a conservative treatment and 11 of the remaining 12 papers suggested that conservative treatment was suitable for some stable fractures. The classification of Effendi et al. modified by Levine and Edwards was used widely. Most hangmans fractures could be managed successfully with traction and external immobilization, especially in Effendi Type I, Type II and Levine-Edwards Type II fractures. It is necessary for Levine-Edwards Type IIa and III fractures to be treated with rigid immobilization. Only for some stable Type I and Levine-Edwards Type II injuries, nonrigid external fixation alone was sufficient. Rigid immobilization alone was necessary for most cases. Surgical stabilization is recommended in unstable cases when there is the possibility of later instability, such as Levine-Edwards Type IIa and III fractures with significant dislocation. The classification system proposed by Effendi et al. and modified by Levine and Edwards provided a clinically reasonable guideline for successful management of hangmans fractures.     

Successful Treatment of Fournier’s Gangrene with the Assistance of Preoperative Computed Tomography in an Elderly Man: Report of a Case

An 87-year-old man presented with inguinal pain and swelling, and was later diagnosed as having Fourniers gangrene. The information gained from preoperative computed tomography (CT) proved very useful for defining the extent of necrosis, and emergency surgery saved his life. Thus, CT should be performed prior to treatment of Fourniers gangrene, even in an emergency situation.     

The changes in arterial keton bodies during upper abdominal surgery

The relationship between the arterial keton body ratio (AKBR: acetoacetate/-hydroxybutyrate) and the plasma hormone activities were studied under a general anesthesia using enflurane group (group G) and a GO + Epidural group (group E) with continuous glucose loading (10g·hr^–1) during partial gastrectomy. In both groups, the AKBR increased significantly during the operation. The plasma insulin activity was significantly positively correlated with the AKBR and it was negatively correlated with log (-hydroxybutyrate) in both groups. We could not find any significant difference of the AKBR between group G and group E. Our results indicate that the plasma insulin activity affects the arterial keton body ratio and that the AKBR must be evaluated considering the plasma hormone activity, especially insulin activity during the operation.(Ogata M, Obata K, Matsumoto et al.: The changes in arterial keton bodies during upper abdominal surgery. J Anesth 4: 131–137, 1990)     

Benigner hellzelliger Lungentumor (≫Sugar Tumor≪)

Zusammenfassung Es wird ein Fall eines benignen hellzelligen Lungentumors (sugar tumor) bei einem 69jährigen Mann vorgestellt. In der Weltliteratur wurden bisher nur 16 ähnliche Fälle beschrieben. Probleme der Diagnose sowie der Pathogenese werden erörtert.

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Benign clear cell tumor (sugar tumor) of the lungCase report and review of the literature

Summary A case of a benign clear cell tumor of the lung (sugar tumor) in a 69 year old man is presented. The world literature lists only 16 similar cases to date. Problems concerning diagnosis and pathogenesis are discussed.

     

Effects of lead on osteoclast-like cell formation in mouse bone marrow cell cultures

To examine an effect of lead (Pb) on the process of osteoclast-like cell formation from its progenitors, we used a mouse bone marrow culture system in which osteoclast-like multinucleated cells (MNCs) were formed in response to bone-resorbing agents. In a 9-day culture period, Pb dose-dependently stimulated MNC formation over the concentration range 2–10 M, whereas at 40 M Pb, MNC formation declined. In an 11-day culture period, MNC formation reached a maximum at 5 M Pb and decreased with increasing concentration of Pb at 10–40 M. Pb-stimulated MNC formation was inhibited by both indomethacin and SC19220, an antagonist of prostaglandin E₂ (PGE₂) receptor. Pb stimulated the production of PGE₂ in marrow cell cultures, suggesting that Pb-stimulated MNC formation is dependent on the production of PGE₂. 3-Isobutyl-1-methylxanthine potentiated Pb-stimulated MNC formation and 2,5-dideoxyadenosine, an inhibitor of adenylate cyclase, inhibited it. A calcium ionophore A23187 increased Pb-induced MNC formation and verapamil, a calcium channel blocker, depressed it. It is possible that a PGE₂-induced increase in the levels of cyclic adenosine 3,5-monophosphate (cAMP) and calcium ions in marrow cells is involved in Pb-induced MNC formation. Pb and parathyroid hormone showed a synergistic stimulation on MNC formation. From these results, Pb is thought to induce osteoclast-like cell formation by a mechanism involving PGE₂ which increases the intracellular levels of cAMP and calcium ions.     

The Role of Transforming Growth Factor α Formulation on Aspirin-Induced Ulcer Healing and Oxidant Stress in the Gastric Mucosa

Purpose Transforming growth factor (TGF) accelerates wound healing, especially in gastric ulcers. Transforming growth factor can be affected by acid and pepsin in the gastric juice. Oxidative stress also plays a role in the formation of gastric lesions. This study was designed (1) to investigate the effects of microemulsion dosage form on the healing of gastric ulcers, and (2) to determine the relationship between oxidative mechanisms and TGF- during ulcer healing.Methods Gastric ulcers were induced in Wistar rats (male, 200 ± 25g), by 150mg/kg acidified aspirin application. The animals were divided into five groups consisting of 7–11 animals. The rats were killed after ulcer induction with aspirin (acute ulcer), or 2 days after ulcer induction (chronic ulcer), or after the daily application of microemulsion and TGF- for 2 days. The ulcer area was measured planimetrically. Thiobarbituric acid reactive substance, glutathione, and gastric mucus levels of tissues were measured by spectrophotometric methods. The total nitric oxide level was measured by a VCl₃ / Griess assay. Statistical comparisons were made by an analysis of variance and the Mann-Whitney U-test.Results The ulcer area and malondialdehyde level of gastric tissue both decreased and the glutathione level increased to intact gastric tissue levels, while the mucus and total nitric oxide levels increased significantly after the application of intragastric TGF-.Conclusion These findings suggest that TGF- accelerates the healing process after aspirin-induced gastric injury, and a relationship was observed between this application and the oxidative reactions.     

Dexamethasone regulates IL-1β and TNF-α-induced interleukin-8 production in human bone marrow stromal and osteoblast-like cells

We have investigated both constitutive- and cytokine-induced secretion of interleukin-8 (IL-8) and its regulation by dexamethasone and 17-estradiol in normal human bone marrow stromal (HBMS), osteoblast-like cells (hOB), and osteosarcoma MG-63 cells. Although HBMS cells secrete low levels of IL-8 constitutively, treatment with IL-1 and tumor necrosis factor- (TNF-) induced IL-8 secretion. Their effects were synergistic but IL-8 production was not affected by 17-estradiol. Human osteosarcoma MG-63 cells also secreted low levels of IL-8 constitutively; the production was induced by IL-1 and TNF- and was also not affected by 17-estradiol. The magnitude of the response to cytokine stimulation of IL-8 in MG-63 cells was much lower than that of HBMS and hOB cells, indicating differences in response in normal and osteoblastic osteosarcoma cells. Dexamethasone (10^-7 M) significantly inhibited IL-1 plus TNF- stimulated IL-8 production in HBMS, MG-63, and hOB cells. The accumulated results demonstrate that IL-8 is secreted by HBMS, MG-63, and hOB cells, suggesting that IL-8 may play a role in the regulation of bone cell function. These data also emphasize the importance of glucocorticoids in controlling cytokine secretion in HBMS, hOB, and MG-63 cells.     

Receptor function studies in specimens from the proximal human urethra obtained by transurethral resection

Summary During transurethral resection (TUR) for prostatic hyperplasia, specimens were taken from the proximal urethra. Muscle strips thus obtained were mounted in an organ bath and muscle contraction was induced by adding increasing concentrations of noradrenaline (NA), methoxamine (₁-agonist) and clonidine (₂-agonist). NA and methoxamine induced a dose-dependent muscle contraction, but clonidine had no effect. The influence of prazosin (₁-antagonist) and yohimbine (₂-antagonist) on the NA-induced muscle contraction was also evaluated. Both antagonists had an inhibitory effect,which was much more potent with prazosin. The specimens taken during TUR were found to be suitable for in vitro receptor function studies. The -adrenergic receptor function in the proximal human urethra was found to be mainly of the -type.     

Neue Einblicke in die Rolle der Östrogene und ihrer Rezeptoren im Prostatakarzinom

Zusammenfassung In der vorliegenden Übersicht werden neue Befunde über die differenzielle Expression von Östrogenrezeptoren und östrogenregulierter Zielgene in der Prostata und im Prostatakarzinom zusammengefasst und ihre Bedeutung für die Tumorentstehung und Androgenresistenz diskutiert. Die beiden Östrogenrezeptoren und (ER, ER) werden in funktionell unterschiedlichen Kompartimenten des Prostataepithels exprimiert; der ER im Proliferationskompartiment (Basalzellschicht), der ER im Differenzierungskompartiment (sekretorisches Epithel).Bei der malignen Transformation des Prostataepithels (high-grade-prostatische intraepitheliale Neoplasie, HGPIN) verlagert sich die ER-Expression in das Differenzierungskompartiment und vermittelt als Onkogen kanzerogene Effekte auf das Prostataepithel. Der ER, ein potenzieller Tumorsuppressor, geht in der HGPIN partiell verloren, wodurch die protektive Wirkung der Phytoöstrogene auf das transformierte Prostataepithel abgeschwächt wird. Das Prostatakarzinom zeigt unabhängig von Grading und Staging hohe Expressoinsraten des ER. Erst im Stadium der Androgenresistenz geht der androgenregulierte ER partiell verloren. Im Gegensatz zum Mammakarzinom ist die Expression des klassischen ER und des Progesteronrezeptors im Prostatakarzinom ein spätes Ereignis in der Tumorprogression und ist maximal in Metastasen und hormonrefraktären Tumoren ausgeprägt. Etwa 30% der metastasierten und androgeninsensitiven Prostatakarzinome zeigen hohe Expressionsraten des ER regulierten Progesteronrezeptors. Das Antiöstrogen Raloxifen wirkt in androgeninsensitiven Prostatakarzinomzelllinien wachstumsinhibitorisch und induziert dosisabhängig den programmierten Zelltod.Aufgrund dieser Befunde sind Patienten mit androgeninsensitiven Prostatakarzinomen potentielle Kandidaten für eine Antiöstrogen- bzw. Antigestagentherapie. Klinische Studien müssen die Effizienz einer solchen Therapie prüfen.     

Comparison of adrenoceptor subtype expression in porcine and human bladder and prostate

We have quantified and characterized ₁-, ₂-and -adrenoceptor subtypes in porcine bladder detrusor and bladder neck, human bladder detrusor, and porcine and human prostate. ₁-, ₂- and -adrenoceptor were identified in radioligand binding studies using [³H]prazosin, [³H]RX 821002 and [¹²⁵I]iodocyanopindolol, respectively, as the radioligands. In porcine male and female detrusor and bladder neck and male prostate, adrenoceptors were detected in the order of abundance > _{2 1} (not detectable), with no major differences between the sexes or between detrusor and bladder neck. In human detrusor and prostate the order of abundance was > _{2 1} (not detectable) and ₁ > ₂. respectively. The ₂-adrenoceptors in all tissues were homogeneously of the _2A-subtype as evidenced by competition binding studies with yohimbine, prazosin, ARC 239 and oxymetazoline. The -adrenoceptors represented a mixed population with a dominance of the ₂-subtype in all tissues as demonstrated by competition binding with ICI 118,551 and CGP 20,712A. We conclude that pigs may be a suitable model for studies of detrusor function with respect to adrenoceptor expression. They may be less suitable for studies of bladder neck or prostate function.