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Biomedical subjects

G J Christ

Publications and source records attributed to G J Christ.

At least 37 records · Page 2Linked to original sources
PubMed2000

The genetics and immunology of Peyronie's disease.

Peyronie's disease (PD) is a condition characterized by localized and often progressive fibrosis and scarring of the penis. This condition has an unknown etiology although several hypotheses have been proposed. These include traumatic, immunologic and genetic causes. We studied the genetics and immunology of PD using both molecular biologic and molecular genetic techniques. Men (n=283) with PD were identified by retrospective chart review of one physician's office practice. These men were contacted by telephone and asked to submit to an interview and blood test for genetic studies. Simultaneously, tissue and cells collected in the laboratory were examined by Western and Northern blot analysis for examination of protein and RNA for expression of HLA. Of the first 107 men contacted, 24 were available and consented to interview and blood testing. The mean age was 60.3 y with an average duration of PD of 4.9 y. One patient had a family history of PD while no patients had Dupuytren's contracture. Twenty patients were considered to have primary disease while four were secondary. Eleven patients had tissue prepared for Northern blot analysis and nine patients were the subject of Western blot analysis. All tissue, both Peyronie's and control expressed class I MHC while no tissue expressed class II MHC. The expression of mRNA of class I MHC was equal for Peyronie's and control patients while the expression at the protein level was less in the PD patients. We conclude that PD may have multiple etiologic agents. One cannot exclude a class II MHC association but in our population, HLA DQ is not expressed. Class I MHC may be involved as the expression of class I MHC protein is different in Peyronie's patients than in controls. Genetic studies are ongoing. International Journal of Impotence Research (2000) 12, Suppl 4, S127-S132.

Aged↗
PubMed2000

Trypanosoma cruzi infection (Chagas' disease) of mice causes activation of the mitogen-activated protein kinase cascade and expression of endothelin-1 in the myocardium.

Chagas' disease, caused by the parasite Trypanosoma cruzi, is an important cause of heart disease. Previous studies from this laboratory revealed that microvascular spasm and myocardial ischemia were observed in infected mice. Infection of endothelial cells with this parasite increased the synthesis of biologically active endothelin-1 (ET-1). Therefore. in the myocardium of T. cruzi-infected mice, we examined ET-1 expression and the p42/44-mitogen activated protein kinase (MAPK)-AP-1 pathway that regulates the expression of ET-1. There was parasitism and myonecrosis in the myocardium of infected C57BL/6 mice. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed elevated mRNA expression of transcription factor AP-1 (c-jun and c-fos) and increased AP-1 DNA binding activity as determined by electrophoretic mobility shift assay (EMSA). Western blot analysis demonstrated an increase in the phosphorylated forms of extracellular signal-regulated kinase (ERK1/2). ET-1 mRNA was upregulated in the myocardium of infected mice. Immunohistochemical and immunoelectron microscopy using anti-ET-1 antibody detected increased expression in cardiac myocytes and endothelium of these mice. These data suggest that ET-1 contributes to chagasic cardiomyopathy and that the mechanism of the increased expression of ET-1 is a result of the activation of the MAPK pathway by T. cruzi infection.

Animals↗
PubMed2000

Differential ICP responses elicited by electrical stimulation of medial preoptic area.

Recent findings indicate a complex role for the medial preoptic area (MPOA) in modulating penile erection. To further investigate this important area we measured changes in intracavernous pressure (ICP) elicited by electrical stimulation of the MPOA and evaluated the contribution of the cavernous nerve to the ICP responses after bilateral transection of the cavernous nerve (CN). In all experiments electrical stimulation was performed unilaterally in anesthetized male rats. Two distinct patterns of ICP response were seen after electrical stimulation of the MPOA: 1) increases in ICP during electrical stimulation (pattern 1, n = 10 rats) and 2) increases in ICP after electrical stimulation was terminated (pattern 2, n = 10 rats). For pattern 1, increases in ICP during stimulation exhibited a stable plateau without contraction of striated penile muscles, and bilateral transection of the CN eliminated the ICP responses. For pattern 2, increases in ICP observed after stimulation were lower, more variable, and accompanied by significant amplitude variations ("peaks"), caused by contraction of striated penile muscles. Bilateral transection of the CN eliminated the pattern 2 ICP response but did not alter striated muscle contraction. Histological studies documented that pattern 1 and pattern 2 responses occurred via electrical stimulation of the anterior and posterior areas of the MPOA, respectively. Thus both responses appear to result from activation of the CN, but the pattern 2 response apparently involves contraction of the striated penile muscles as well.

Animals↗
PubMed2000

Biophysical characteristics of gap junctions in vascular wall cells: implications for vascular biology and disease.

The role gap junction channels play in the normal and abnormal functioning of the vascular wall is the subject of much research. The biophysical properties of gap junctions are an essential component in understanding how gap junctions function to allow coordinated relaxation and contraction of vascular smooth muscle. This study reviews the properties thus far elucidated and relates those properties to tissue function. We ask how biophysical and structural properties such as gating, permselectivity, subconductive states and channel type (heteromeric vs homotypic vs heterotypic) might affect vascular smooth muscle tone.

Biophysical Phenomena↗
PubMed2000

Gap junctions in isolated rat aorta: evidence for contractile responses that exhibit a differential dependence on intercellular communication.

Connexin43 (Cx43) is a major gap junction protein present in the Fischer-344 rat aorta. Previous studies have identified conditions under which selective disruption of intercellular communication with heptanol caused a significant, readily reversible and time-dependent diminution in the magnitude of alpha1-adrenergic contractions in isolated rat aorta. These observations have indentified a significant role for gap junctions in modulating vascular smooth muscle tone. The goal of these steady-state studies was to utilize isolated rat aortic rings to further evaluate the contribution of intercellular junctions to contractions elicited by cellular activation in response to several other vascular spasmogens. The effects of heptanol were examined (0.2-2.0 mM) on equivalent submaximal ( approximately 75% of the phenylephrine maximum) aortic contractions elicited by 5-hydroxytryptamine (5-HT; 1-2 microM), prostaglandin F2alpha (PGF2alpha; 1 microM) and endothelin-1 (ET-1; 20 nM). Statistical analysis revealed that 200 microM and 500 microM heptanol diminished the maximal amplitude of the steady-state contractile responses for 5-HT from a control response of 75 +/- 6% (N = 26 rings) to 57 +/- 7% (N = 26 rings) and 34.9 +/- 6% (N = 13 rings), respectively (P<0.05), and for PGF2alpha from a control response of 75 +/- 10% (N = 16 rings) to 52 +/- 8% (N = 19 rings) and 25.9 +/- 6% (N = 18 rings), respectively (P<0.05). In contrast, 200 microM and 500 microM heptanol had no detectable effect on the magnitude of ET-1-induced contractile responses, which were 76 +/- 5. 0% for the control response (N = 38 rings), 59 +/- 6.0% in the presence of 200 microM heptanol (N = 17 rings), and 70 +/- 6.0% in the presence of 500 microM heptanol (N = 23 rings) (P<0.13). Increasing the heptanol concentration to 1 mM was associated with a significant decrease in the magnitude of the steady-state ET-1-induced contractile response to 32 +/- 5% (21 rings; P<0.01); further increasing the heptanol concentration to 2 mM had no additional effect. In rat aorta then, junctional modulation of tissue contractility appears to be agonist-dependent.

Animals↗
PubMed2000

K+ channels and gap junctions in the modulation of corporal smooth muscle tone.

Changes in the contractile status (i.e., contraction and relaxation) of corporal and arterial smooth muscle cells (myocytes) govern the flow of blood to and from the penis and, thus, ultimately have a major impact on erectile capacity. As with many other smooth muscle cell types, corporal myocyte contractility is inextricably linked to ion channel activity. Corporal smooth muscle cells possess a rich repertoire of ion channels, including calcium, chloride and potassium channels, as well as gap junction (intercellular) channels. Among these, the K(ATP) (i.e., the metabolically regulated K(+) channel) and the K(Ca) (i.e., maxi-K or large conductance, calcium-sensitive K(+) channel) nonjunctional channel subtypes, as well as connexin43-derived gap junction (intercellular) channels, are thought to be particularly relevant to the control of corporal myocyte contractility. In fact, whereas K(+) channels are an important convergence point for modulating cellular function, gap junctions are a major conduit for ensuring coordinated cellular, and thus tissue, function. The evidence documenting the presence and physiological relevance of K(+) channels and gap junctions to human erectile physiology and function is reviewed. Finally, one potentially revolutionary therapeutic strategy that takes advantage of the important contribution of K(+) channels and gap junctions to erectile physiology is described: maxi-K ion channel (gene) therapy.

Journal Article↗
PubMed1999

Analysis of the presence and physiological relevance of subconducting states of Connexin43-derived gap junction channels in cultured human corporal vascular smooth muscle cells.

Subconductance states are a commonly observed feature of gap junction channels. Their overt frequency and consistent appearance in both single and multichannel records have led to speculation that they might be of physiological importance in terms of altering the rate of small solute transfer from cell to cell. Among the connexin gene family, connexin43 (Cx43) is the most ubiquitous connexin that has been shown to generate subconductive states. Therefore, it was the explicit aim of this investigation to more fully evaluate the potential contribution of human Cx43-derived subconducting states to intercellular communication in cultured human corporal vascular smooth muscle cells. To determine the weight of subconductive states in our records, we analyzed amplitude histograms of multichannel and single-channel data during the application of transjunctional voltages larger than expected for physiological conditions but still smaller than transjunctional voltages known to induce lower conductive states (Vo>Vj). The data clearly indicated that the subconducting states occupy only a small fraction of the total channel open time. This was reflected by the fact that the average open probability for the subconductive state(s) determined from the 9 records analyzed was approximately 2%. Closer inspection of the data revealed that the frequency of subconductive states was actually higher than the frequency of the main state conductance. In summary, recording conditions sufficient for evaluation of the intrinsic gating characteristics of human Cx43-derived gap junction channels have been used. Under these conditions, our data clearly indicate that despite their greater frequency, the duration of subconductance events is so short relative to the main state duration as to render them physiologically insignificant.

Cells, Cultured↗
PubMed1999

The effects of alterations in nitric oxide levels in the paraventricular nucleus on copulatory behavior and reflexive erections in male rats.

PURPOSE: To examine the effects of altered nitric oxide (NO) levels in the paraventricular nucleus (PVN) on copulatory behavior and reflexive erections in male rats. MATERIALS AND METHODS: Extracellular nitrite (NO2-) and nitrate (NO3-) levels were measured in the PVN following administration of the NO precursor L-arginine (L-arg, 10 mM), the NO synthase inhibitor N(G)-monomethyl L-arginine (L-NMMA, 10 mM), or Ringer's solution via a dialysis probe to the PVN. The effects of alterations in extracellular NO on reflexive erections and copulatory behavior were assessed. RESULTS: L-arg administration was associated with significant elevations of extracellular NO2- and NO3- in the PVN, while L-NMMA significantly reduced NO2- and NO3- levels. A corresponding increase in reflexive erections was noted during infusion of L-arg in the PVN, with a corresponding decrease in reflexive erections observed during administration of L-NMMA into the PVN (Student's t test for paired samples, p <0.05). Mount rate was unaffected by infusion of the either L-arg or L-NMMA. CONCLUSIONS: Altered NO levels in the PVN affected the frequency of reflexive erections, but not the mount rate. These studies contrast with previous observations of the effects of altered NO levels in the MPOA, and support the hypothesis that physiological specificity in the actions of NO on discrete brain nuclei may have important implications to erectile physiology and dysfunction.

Animals↗
PubMed1999

A stretch-sensitive Cl- channel in human corpus cavernosal myocytes.

With the patch clamp method we demonstrate a stretch-sensitive Cl- currents as well as stretch-sensitive Cl- channels in a small group (5%,n 117) of cultured human corpus cavernosal muscle cells. The current and the channel activities had the following characteristics: (1) Their equilibrium potentials changed with extracellular Cl- concentration close to that predicted by Nernst equation provided that the relevant channels had high permeability to Cl- but low permeability to acetate ions; (2) They were blocked by mM concentrations of Zn2+; (3) The i-v relation of single channel current was almost linear for holding potentials varied from -70 to +60 mV; and (4) The channels had unitary conductances of approximately 140-170 pS.

Acetates↗
PubMed1999

Characterization of ATP-sensitive potassium channels in human corporal smooth muscle cells.

Potassium (K) channels play a significant role in modulating human corporal smooth muscle tone, and thus, erectile capacity. Recent pharmacological studies indicate that the metabolically-regulated K channel (KATP) may be an important modulator of human penile erection with significant therapeutic potential. The goal of these initial studies, therefore, was to utilize patch clamp techniques to characterize the putative KATP subtype(s) present in cultured and freshly isolated human corporal smooth muscle cells. In the cell-attached patch mode, two distinct unitary K+ currents were identified whose respective conductance values were similar in cultured and freshly isolated smooth muscle cells. In cultured myocytes, the measured conductance values in symmetric KCl (140 mM) solutions were 59.1 +/- 2.7 pS and 18.4 +/- 2.1 pS (n = 5 cells). Under identical experimental conditions in freshly isolated myocytes, corresponding conductance values were 59.2 +/- 3.7 pS and 18.5 +/- 2.4 pS, respectively (n = 4 cells). I-V curves constructed during step depolarization (-60 to +80 mV), revealed a linear I-V relationship for both unitary conductances. Single channel records documented that both conductances were reversibly inhibited by the application of ATP (1-3 mM) to the bath solution in the inside-out attached patch configuration. The unitary activity of both K channel subtypes was significantly increased by the application of pinacidil (10 microM) and levcromakalim (10 microM). Whole cell patch recordings documented a glibenclamide-sensitive, pinacidil- and levcromakalim-induced increase in the whole cell outward K+ current during step depolarization (-70 mV to +130 mV) of 105 +/- 37%, 139 +/- 42%, respectively. These data confirm and extend our previous observations, and provide the first evidence for the presence of KATP channel subtypes in human corporal smooth muscle cells.

Adenosine Triphosphate↗
PubMed1999

Prostaglandin E1 activates the large-conductance KCa channel in human corporal smooth muscle cells.

The large conductance calcium-sensitive potassium channel (KCa or maxi-K) is an important modulator of human corporal smooth muscle tone, and therefore, erectile capacity. The goal of this investigation was to evaluate the actions of prostaglandin E1 (PGE1), the most widely used and effective drug for the treatment of impotence, on the activity of the KCa channel, a prominent K+ current present in human corporal smooth muscle. Whole-cell patch clamp studies conducted on short-term cultured and enzymatically dissociated human corporal smooth muscle cells, revealed mean resting potentials of -50.8 +/- 2.1 mV (n = 8) and -34 +/- 4 mV (n = 8), respectively. In the attached-patch configuration, the corresponding single-channel slope conductance values for the KCa channel subtype were 173 +/- 4 pS (n = 8) in cultured cells, and 190 +/- 13 pS (n = 3) in freshly isolated myocytes. Furthermore, voltage clamp experiments revealed that relative to control values, the application of PGE1 to cultured cells (3.3 or 33 microM) elicited an apparent increase in both the open probability (Po; ranging from 1.2-23 fold), and the mean open time (5-6 fold) of the KCa channel at membrane potentials of +90 mV and +110 mV. PGE1-induced alterations in KCa channel activity were also observed in freshly isolated corporal myocytes. In the whole cell-recording mode, statistically significant, Charybdotoxin-sensitive (100 nM) 2-3 fold increases in the outward K+ currents were observed in both cultured and freshly isolated corporal myocytes. The presence of a PKA inhibitor (fragment 6-22 amide; 10 microM) in the pipette tip was also associated with a nearly complete ablation of the observed PGE1-induced whole cell K+ currents. Taken together, these data confirm and extend our previous observations, and indicate that PGE1-induced relaxation of human corporal smooth muscle is related, at least in part, to activation of the KCa channel subtype resulting in cellular hyperpolarization.

Alprostadil↗
PubMed1999

Intraoperative electrical stimulation of cavernosal nerves with monitoring of intracorporeal pressure in patients undergoing nerve sparing radical prostatectomy.

OBJECTIVE: To explore the utility of intraoperative cavernosal nerve stimulation in facilitating atraumatic nerve dissection during radical prostatectomy, and thus help predict postoperative erectile function. PATIENTS AND METHODS: Fourteen patients (aged 51-72 years) underwent nerve-sparing radical retropubic prostatectomy (NSRRP); 10 were potent before surgery (group 1), and four had erectile dysfunction (group 2). A multi-acquisition system (MacLab/8e) with a Macintosh computer was used for real-time display and recording of intracavernosal pressure (ICP) during surgery. Nerves were stimulated with a bipolar probe (monophasic rectangular pulses, 10 mA, 20 Hz, 0.22 s) before and after removal of the gland. The follow-up consisted of interviews with patients and their partners' 12-18 months after treatment. RESULTS: The mean (sem) basal ICP of 8. 0 (2.0) cmH2O remained unchanged during nerve dissection. The mean increase in ICP during electrical stimulation was >50 cmH2O in seven potent patients (group 1) and was sustained as long as the nerve was stimulated. Postoperatively, these seven patients reported erections sufficient for sexual intercourse. However, the three remaining patients in group 1 had pressure rises of <30 cmH2O, of whom two reported partial erections and one reported total impotence postoperatively. The recovery time for erectile function was 6-12 months after surgery. Two patients from group 2 had transient increases in ICP to <40 cmH2O; one had an increase to 20 cmH2O and one had no response at all. All four patients remained totally impotent postoperatively. There were no complications. CONCLUSIONS: Intraoperative electrical stimulation of the cavernosal nerves with ICP monitoring before and after NSRRP is a safe and reliable method for documenting nerve continuity and its functional status. Patients who have normal preoperative erectile function and show an adequate rise in ICP upon electrical nerve stimulation during NSRRP will almost certainly be potent after surgery. This tool may be used to facilitate atraumatic nerve dissection during NSRRP.

Aged↗
PubMed1999

Further evidence for the selective disruption of intercellular communication by heptanol.

The lack of selective gap junctional uncoupling agents has hampered evaluation of the contribution of intercellular communication to pharmacomechanical coupling and vascular contractility. Thus we further explored the utility and selectivity of heptanol as a gap junctional uncoupling agent in isolated rat aortic rings. Fifty-two aortic rings were obtained from 15 rats and were precontracted to approximately 75% of maximum with phenylephrine (PE). When contraction achieved steady state (approximately 5 min), a single concentration of heptanol (200 microM) was added to each aortic ring at 1- to 3-min intervals for up to 42 min post-PE addition. At early time points (5-10 min after PE), heptanol elicited an approximately 50% loss of tension (i.e., relaxation). At subsequent time points post-PE, a gradual and time-dependent decrease in the magnitude of the heptanol-induced relaxation was observed until, after approximately 40 min, addition of heptanol was associated with little, if any, detectable relaxation. Linear regression analysis of the magnitude of the heptanol-induced relaxation vs. the square root of the elapsed time interval (from addition of PE) revealed a highly significant negative correlation (P < 0.001, R = 0.81). Studies conducted on KCl-precontracted aortic rings revealed no detectable heptanol-induced relaxation after development of the steady-state KCl-induced contraction. These data extend our previous observations to further document the potential utility of heptanol as a "relatively selective" uncoupling agent.

Animals↗
PubMed1999

Sildenafil: a new oral therapy for erectile dysfunction.

Sildenafil citrate (Viagra) is a relatively selective 5-phosphodiesterase (PDE) inhibitor. It is the first oral medication approved for the treatment of erectile dysfunction (ED). The neuronal release of NO which binds to the heme-containing region of guanylate cyclase increases levels of cGMP. This leads to a cascade of reaction which results in corporal smooth muscle relaxation and penile erection. Sildenafil causes an erection by inhibiting PDE5, which in turn causes an increase in the intracellular levels of cGMP. Sildenafil is well absorbed after a single oral administration with a t(1/2) of approximately 4 h. The mode of onset varies from 0.5-4 h. The drug has been used in millions of men since first approved by the U.S. FDA 1 year ago and has revolutionized the approach to, and therapy of, erectile dysfunction.

Journal Article↗
PubMed1999

The putative mechanistic basis for the modulatory role of endothelin-1 in the altered vascular tone induced by Trypanosoma cruzi.

Chagas' disease, caused by Trypanosoma cruzi, is an important cause of heart disease in Latin America. T. cruzi-induced microvascular compromise, in turn, is thought to play a major role in chagasic heart disease. Previous in vitro studies have implicated endothelin-1 (ET-1) as a potentially important vasomodulator present in increased levels in the supernatant of T. cruzi infected cultured human umbilical vein endothelial cells (HUVEC). Thus, the goal of the present investigation was to further evaluate the potentially important contribution of ET-1 to T. cruzi-induced alterations in vascular tone in vitro. Bioassay studies once again documented that exposure of isolated rat aortic rings to infected HUVEC supernatants elicited contractile responses whose steady-state magnitude was significantly greater than contractile responses elicited by exposure of aortic rings to uninfected HUVEC supernatants. Furthermore, the increased aortic contractility was significantly attenuated by the presence of the ET(A) subtype selective antagonists BMS-182,874 or BQ-123. Additionally, incubation of HUVEC with either verapamil or phosphoramidon prior to infection was also associated with reduced aortic contractility, upon exposure to the supernatant. Phosphoramidon, but not verapamil, produced a significant decrease in the measured ET-1 levels in the HUVEC supernatant. Consistent with the bioassay results, preincubation of Fura-2-loaded cultured rat aortic vascular smooth muscle cells with verapamil resulted in a near complete ablation of ET-1-induced transmembrane Ca2+ flux. Taken together, these data are consistent with the hypothesis that ET-1-induced vasoconstriction may play an important modulatory role in the vascular compromise characteristic of T. cruzi infection.

Animals↗
PubMed1998

Neuronal innervation, intracellular signal transduction and intercellular coupling: a model for syncytial tissue responses in the steady state.

A model tissue is proposed in which chemically responsive cells are interconnected by gap junctions and innervated by the autonomic nervous system. The model is explicitly dependent on the following physiologically relevant assumptions: (1) a fraction of the cells are directly innervated, and these cells respond to a periodic neuronal stimulus (i.e. the release of neurotransmitter) by production of an intracellular substance (i.e. second messenger molecule); (2) production of second messenger molecules modulates the amplitude of a cellular response, such as contraction or secretion; (3) intracellular formation of second messenger molecules in innervated cells is proportional to the periodicity of the neuronal stimulus, while the intracellular concentration in non-innervated cells is governed by the half-life of the second messenger molecule and the extent of cell-to-cell coupling; (4) the amplitude of the graded response of the individual cell is related to the intracellular second messenger concentration by a Michaelis-Menten function; (5) the amplitude of the graded tissue response is a function of the innervation density, the frequency of stimulation, and the extent of intercellular coupling. Thus, a stimulus-response relationship was developed, where the magnitude of the tissue response was described as a function of the total tissue stimulus. The predicted stimulus-response curve was encapsulated by two parameters: (1) the Hill-exponent, which reflects the steepness of the stimulus-response curve; and (2) the location of the stimulus-response curve, or the half-maximally effective stimulus. Both random and uniform neuronal innervation patterns were considered in model tissues with various effective dimensions. The simulations were also applied to a realistic model of vascular tissue. The shape of the stimulus-response curve is critically dependent on the geometry of innervation. For physiologically relevant (10-90% over 2-3 orders of magnitude) dose-response curves, the model yields an implicit relationship between three different dimensionless parameters. If, in a system, two of these parameters are known, the model can be used to bracket the possible range of the third parameter.

Animals↗
PubMed1998

Molecular studies of human connexin 43 (Cx43) expression in isolated corporal tissue strips and cultured corporal smooth muscle cells.

Intercellular communication plays an important role in erectile function. The goal of this study, therefore, was two-fold. Firstly, to determine if cultured corporal smooth muscle cells provide a valid model system for evaluating the role of junctional communication to erectile physiology, and secondly, to explore the possibility that there may be age-related alterations in Cx43 mRNA expression. Human corpus cavernosum tissue was obtained from 31 patients with a mean age of 58 (range 27-89), while cell cultures were developed from 21 distinct patients with a mean age of 57 (range 26-59). Northern blots revealed that mRNA for Cx43 was expressed at detectable levels in all samples examined. It migrated as a transcript with an apparent size of 3.1 Kb. Western blots revealed the presence of multiple bands of Cx43 protein in both tissues and cells. However, Cx43 protein in tissue predominantly migrated as a 45 kDa band, while the Cx43 from cultured cells predominantly migrated as 41 kDa band. Cx43 mRNA expression was similarly heterogeneous in both frozen tissues and cultured cells. An approximately 3-5-fold increase in Cx43 mRNA levels was observed in cultured cells relative to frozen tissue, but the expression of Cx43 mRNA was not further altered upon passaging (p1-5). When Cx43 mRNA levels were normalized, and expressed as a ratio of the Cx43/beta-tubulin mRNA, there was a significant negative correlation between patient age and Cx43 levels on frozen tissues, but not on cultured cells. We conclude that: (1) There is similar heterogeneity/variability in Cx43 mRNA levels in frozen tissues and cultured cells derived from human corpus cavernosum. (2) That the expression of Cx43 mRNA in cultured cells is sufficiently stable, and similar to, expression levels in tissue as to provide a valid and physiologically relevant model system for further studying the role(s) of Cx43 in the regulation of penile erection. (3) There is a statistically significant, albeit modest, negative correlation between the Cx43/beta-tubulin ratio and patient age in frozen corporal tissue strips, but not on cultured corporal smooth muscle cells. Such observations provide further evidence for the plasticity of intercellular communication in the erectile process. Moreover, the similarities in the apparent regulation of Cx43 mRNA levels and that of the putative 'housekeeping' gene beta-tubulin, may suggest that Cx43 is constitutively synthesized in this tissue.

Adult↗