Guinea Pig Prostate Research Articles

Involvement of prostatic interstitial cells of Cajal in inflammatory cytokines-elicited catecholamines production: Implications for the pathophysiology of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)

In a previous work using guinea pig prostate, we have identified a novel interstitial cells of Cajal (ICCs) which possess close contacts between sympathetic nerve bundles and smooth muscle cells. The ability of prostatic ICCs in mediating excitatory neural inputs was therefore studied using isolated murine prostate ICCs by collagenase digestion combined with FACS method. RT-PCR and Western blotting analyses revealed that prostatic ICCs under a quiescent state expressed abundantly the rate-limiting enzymes essential for catecholamine synthesis. Moreover, distinct proinflammatory cytokines (e.g. IL-1β, IL-8, ICAM-1 and TNF-α) could significantly stimulate the expression levels of the rate-limiting enzymes of catecholamine production in prostate ICCs. Mechanistically, the above-mentioned stimulatory effects of proinflammatory cytokines appeared to be mediated via activation of NF-κB, HIF-1α and HDACs signaling pathways. Considering that prostatic catecholamine overactivity serves as an essential etiology of pelvic pain by indirectly stimulating the smooth muscle cell proliferation, or by directly causing muscular spasm, our results collectively suggest that targeting the NF-κB, HIF-1α and HDACs pathways in prostate ICCs be considered as a new strategy for treatment of chronic pelvic pain syndrome (CPPS) induced by chronic prostatitis (CP). Overall, the current study should shed novel light on the biology of this unique prostate ICCs.

Electrical properties of purinergic transmission in smooth muscle of the guinea-pig prostate.

Prostatic smooth muscle develops spontaneous myogenic tone which is modulated by autonomic neuromuscular transmission. This study aimed to investigate the role of purinergic transmission in regulating electrical activity of prostate smooth muscle and whether its contribution may be altered with age. Intracellular recordings were simultaneously made with isometric tension recordings in smooth muscle preparations of the guinea-pig prostate. Immunostaining for P2X1 receptors on whole mount preparations was also performed. In prostate preparations which generated spontaneous slow waves, electrical field stimulation (EFS)-evoked excitatory junction potentials (EJPs) which were abolished by guanethidine (10 μM), α-β-methylene ATP (10 μM) or pyridoxal phosphate-6-azophenyl-2,4-disulfonic acid (PPADS, 10 μM) but not phentolamine (1 μM). Consistently, immunostaining revealed the expression of P2X1 receptors on prostatic smooth muscle. EJPs themselves did not cause contractions, but EJPs could sum to trigger a slow wave and associated contraction. Yohimbine (1 μM) and 3,7-dimethyl-1-propargylxanthine (DMPX, 10 μM) but not propranolol (1 μM) potentiated EJPs. Although properties of EJPs were not different between young and aging guinea-pig prostates, ectoATPase inhibitor ARL 67156 (100 μM) augmented EJP amplitudes by 64.2 ± 29.6% in aging animals, compared to 22.1 ± 19.9% in young animals. These results suggest that ATP released from sympathetic nerves acts on P2X1 purinoceptors located on prostate smooth muscle to evoke EJPs, while pre-junctional α2-adrenergic and adenosine A2 receptors may play a role in preventing excessive transmitter release. Age-related up-regulation of enzymatic ATP breakdown may be a compensatory mechanism for the enhanced purinergic transmission which would cause hypercontractility arising from increased ATP release in older animals.

Voltage‐operated Ca2+ currents and Ca2+‐activated Cl– currents in single interstitial cells of the guinea‐pig prostate

To investigate the expression of 'T-type' and 'L-type' voltage-operated Ca(2) (+) channels in single interstitial cells of the guinea-pig prostate. Whole-cell and perforated patch-clamp techniques were applied to prostatic interstitial cells (PICs) dispersed using collagenase. In contrast to prostatic myocytes, PICs under voltage clamp and filled with K(+) (130 mm) were distinguished by the absence of a voltage-operated transient outward K(+) current or spike discharge upon membrane depolarisation when under current clamp. Depolarisation of Cs(+) -filled PICs evoked an inward current at potentials positive to -60 mV, which peaked in amplitude near 0 mV. This inward current increased when Ba(2+) (5 mm) replaced the external Ca(2) (+) (1.5 mm) and displayed a variable sensitivity to the inhibitory actions of conditioning depolarisations to -40 mV applied before the test depolarisation or to 1 μm nifedipine, the 'L-type' Ca(2) (+) channel blocker. A residual inward current recorded in nifedipine was blocked by 10 μm Ni(2) (+) . Cs(+) -filled PICs also displayed a slowly inactivating outward current that was little affected by nifedipine, reduced by the Cl(-) channel blocker, niflumic acid (10 μm) and blocked by Ba(2) (+) or a conditioning depolarisation. PICs express both a small 'T-type' Ca(2) (+) channel current (ICa ) and a large 'L-type' ICa . Ca(2) (+) influx through 'T-type' ICa was an essential trigger for the activation of a Ca(2) (+) -activated Cl(-) -selective current. The dependence of PIC Ca(2) (+) signalling on 'T-type' and 'L-type' ICa is unique compared with other interstitial cells of the urogenital tract and may well be pharmaceutically exploitable.

This Month in Investigative Urology

No AccessJournal of UrologyThis Month in Investigative Urology1 Oct 2014This Month in Investigative Urology Karl-Erik Andersson Karl-Erik AnderssonKarl-Erik Andersson More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.07.006AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "This Month in Investigative Urology." The Journal of Urology, 192(4), pp. 1011–1012 References 1 : Voltage dependence of slow wave frequency in the guinea pig prostate. J Urol2014; 192: 1286. Link, Google Scholar 2 : Shock wave lithotripsy targeting of the kidney and pancreas does not increase the severity of metabolic syndrome in a porcine model. J Urol2014; 192: 1257. Link, Google Scholar 3 : Elevated serum IgE may be associated with development of ketamine cystitis. J Urol2014; 192: 1249. Link, Google Scholar © 2014 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 192Issue 4October 2014Page: 1011-1012 Advertisement Copyright & Permissions© 2014 by American Urological Association Education and Research, Inc.MetricsAuthor Information Karl-Erik Andersson More articles by this author Expand All Advertisement PDF downloadLoading ...

Voltage Dependence of Slow Wave Frequency in the Guinea Pig Prostate

Spontaneous phasic contractions of the guinea pig prostate stroma result from the generation of slow waves that appear to primarily rely on spontaneous Ca(2+) release from the endoplasmic/sarcoplasmic reticulum and subsequent opening of Ca(2+) activated chloride channels. We investigated voltage dependent mechanisms in the regulation of slow wave frequency. Changes in membrane potential were recorded using conventional intracellular recording techniques while simultaneously measuring the isometric tension of guinea pig prostate lobes. Fluorescence immunohistochemistry was done to determine the cellular composition of the prostate stroma. Depolarization induced by high K(+) solution, K(+) free solution or outward current injection was associated with increased slow wave frequency. In contrast, hyperpolarization induced by the re-addition of K(+), adenosine triphosphate sensitive K(+) channel openers or inward current injection prevented slow wave generation. K(+) channel openers induced hyperpolarization and thecessation of slow waves was reversed by glibenclamide (10 μM). Nifedipine (1to 10 μM) shortened the duration of slow waves and pacemaker potentials butoften failed to prevent their generation and associated contractions. Subsequently Ni(2+) (100 μM) or mibefradil (1 μM) largely suppressed slow waves and abolished residual contractions. Immunohistochemistry revealed small interconnected smooth muscle bundles as well as vimentin positive interstitial cells but failed to show a network of Kit positive interstitial cells. Prostate slow wave frequency is voltage dependent due to the significant contribution of L-type and T-type Ca(2+) channels. Prostate slow waves may arise from cooperation between spontaneous Ca(2+) release from internal stores and plasmalemmal voltage dependent Ca(2+) channels.

Tamsulosin modulates, but does not abolish the spontaneous activity in the guinea pig prostate gland

To examine the effects of the α1A -adrenoceptor antagonist, tamsulosin, on spontaneous contractile and electrical activity in the guinea-pig prostate gland. The effects of tamsulosin (0.1 and 0.3 nM) were investigated in adult and ageing male guinea pig prostate glands using conventional tension recording and electrophysiological intracellular microelectrode recording techniques. Tamsulosin reduced spontaneous activity, and had different age-dependent effects on adult and ageing guinea pigs at different concentrations. 0.1 nM tamsulosin caused a significantly greater reduction of spontaneous contractile and electrical activity in ageing guinea pigs in comparison to adult guinea pigs. In contrast, 0.3 nM tamsulosin had a significantly greater reduction of spontaneous contractile and electrical activity in adult guinea pigs in comparison to ageing guinea pigs. This study demonstrates that tamsulosin can modulate spontaneous myogenic stromal contractility and the underlying spontaneous electrical activity; tamsulosin does not block spontaneous activity. This reduction in spontaneous activity suggests that downstream cellular mechanisms underlying smooth muscle tone are being targeted, and these may represent novel therapeutic targets to better treat benign prostatic hyperplasia.

Purinergic signalling during neuromuscular transmission of the guinea-pig prostate

The prostate exhibits two types of contractions: coordinated, neurogenic contractions that facilitate ejaculation while spontaneous myogenic activity provides small amplitude contractions that can prevent the stagnation of prostatic fluids. The prostate is sympathetically innervated but our studies find that purinergic signalling as well as cholinergic innervation may also play a role in facilitating prostate contractility.

Effects of imatinib mesylate on the spontaneous activity generated by the guinea-pig prostate

What's known on the subject? and what does the study add?: Several studies have examined the functional role of tyrosine kinase receptors in the generation of spontaneous activity in various segments of the gastrointestinal and urogenital tracts through the application of its inhibitor, imatinib mesylate (Glivec®), but results are fairly inconsistent. This is the first study detailing the effects of imatinib mesylate on the spontaneous activity in the young and ageing prostate gland. As spontaneous electrical activity underlies the spontaneous rhythmic prostatic contractions that occur at rest, elucidating the mechanisms involved in the regulation of the spontaneous electrical activity and the resultant phasic contractions could conceivably lead to the identification of better targets and the development of more specific therapeutic agents to treat prostate conditions. To investigate the effect of imatinib mesylate, a tyrosine kinase receptor inhibitor, in the generation of spontaneous electrical and contractile activity in the young and ageing guinea-pig prostate. Standard tension and intracellular recording were used to measure spontaneous contractions and slow waves, respectively from the guinea-pig prostate at varying concentrations of imatinib mesylate (1-50 μm). Imatinib mesylate (1-10 μm), did not significantly affect slow waves recorded in the prostate of both age groups but at 50 μm, the amplitude of slow waves from the ageing guinea-pig prostate was significantly reduced (P < 0.05, n = 5). In contrast, the amplitude of contractions across all concentrations in the young guinea-pig prostate was reduced to between 35% and 41% of control, while the frequency was reduced to 15.7% at 1 μm (n = 7), 49.8% at 5 μm (n = 10), 46.2% at 10 μm (n = 7) and 53.1% at 50 μm (n = 5). Similarly, imatinib mesylate attenuated the amplitude and slowed the frequency of contractions in ageing guinea-pigs to 5.15% and 3.3% at 1 μm (n = 6); 21.1% and 20.8% at 5 μm (n = 8); 58.4% and 8.8% at 10 μm (n = 11); 72.7% and 60% at 50 μm (n = 5). A significant reduction in contractions but persistence of slow waves suggests imatinib mesylate may affect the smooth muscle contractile mechanism. Imatinib mesylate also significantly reduced contractions in the prostates of younger guinea pigs more than older ones, which is consistent with the notion that the younger guinea-pig prostate is more reliant on the tyrosine-dependent pacemaker ability of interstitial cells of Cajal-like prostatic interstitial cells.

Interstitial cells of Cajal mediate excitatory sympathetic neurotransmission in guinea pig prostate

Morphological and functional studies have confirmed that interstitial cells of Cajal (ICCs) are involved in many enteric motor neurotransmission pathways. Recent investigations have demonstrated that human and guinea pig prostate glands possess a distinct cell type with morphological and immunological similarities to ICCs. These prostate ICCs have a close relationship with nerve bundles and smooth muscle cells. Prostate smooth muscle tone is largely induced by stimulation from the sympathetic nervous system, which releases excitatory norepinephrine (NE) to act on the α1-adrenoceptor. We have performed morphological and functional experiments to determine the role of ICCs in sympathetic neurotransmission in the guinea pig prostate based on the hypothesis that prostate ICCs act as mediators of sympathetic neurotransmission. Immunohistochemistry revealed many close points of contact between ICCs and sympathetic nerve bundles and smooth muscle cells. Double-labeled sections revealed that α1-adrenoceptor and the gap junction protein connexin 43 were expressed in prostate ICCs. Surprisingly, prostate ICCs co-expressed tyrosine hydroxylase and dopamine β-hydroxylase, two markers of sympathetic neurons. Functionally, the application of NE evoked a large single inward current in isolated prostate ICCs in a dose-dependent manner. The inward current evoked by NE was mediated via the activation of α1-adrenoceptors, because it was abolished by the non-specific α-adrenoceptor antagonist, phentolamine and the specific α1-adrenoceptor antagonist, prazosin. Thus, ICCs in the guinea pig prostate are target cells for prostate sympathetic nerves and possess the morphological and functional characteristics required to mediate sympathetic signals.

Involvement of Rho-Kinase Signaling Pathways in Nerve Evoked and Spontaneous Contractions of the Guinea Pig Prostate

Men with benign prostatic hyperplasia commonly experience irritative lower urinary tract symptoms, which are due at least in part to enhanced prostatic smooth muscle tone. To provide some insight into the changes that occur in prostatic contractility with age, we examined the contribution of rho-kinase dependent Ca(2+) sensitization in neurogenic and spontaneous contractions of young and aging guinea pig prostates. We used conventional tension recording and electrophysiological intracellular microelectrode recording techniques. The Rho-kinase inhibitor Y-27632 (10 and 100 μM) significantly inhibited electrical field stimulated evoked (neurogenic) contractions in the guinea pig prostate in a dose dependent manner. In addition, Y-27632 (1 and 10 μM) similarly suppressed tetrodotoxin insensitive spontaneous contractions in dose dependent fashion. While Y-27632 at 10 μM decreased spontaneous contractions of young and aging guinea pig prostates, as evidenced by a significant decrease in the AUC, there was no significant difference in the degree of inhibition between the 2 age groups. In contrast to contractile activity, Y-27632 did not affect the generation or modulation of spontaneous slow wave electrical activity, which underlies spontaneous contractions. There are strong indicators that Rho-kinase signaling pathways have a significant role in prostatic smooth muscle contractility, most likely independent of cytosolic Ca(2+) levels. Features of the rho-kinase pathway may well represent alternative, novel future therapeutic targets to reduce prostatic contractility, thereby alleviating the lower urinary tract symptoms arising from benign prostatic hyperplasia.

Nitric Oxide Signaling Pathways Involved in the Inhibition of Spontaneous Activity in the Guinea Pig Prostate

We investigated nitric oxide mediated inhibition of spontaneous activity recorded in young and aging guinea pig prostates. Conventional intracellular microelectrode and tension recording techniques were used. The nitric oxide donor sodium nitroprusside (10 μM) abolished spontaneous contractions and slow wave activity in 5 young and 5 aging prostates. Upon adding the nitric oxide synthase inhibitor L-NAME (10 μM) the frequency of spontaneous contractile and electrical activity was significantly increased in each age group. This increase was significantly larger in 4 to 8 preparations of younger vs aging prostates (about 40% to 50% vs about 10% to 20%, 2-way ANOVA p<0.01). Other measured parameters, including the duration, amplitude and membrane potential of spontaneous electrical and contractile activity, were not altered from control values. The guanylate cyclase inhibitor ODQ (10 μM) significantly increased the frequency of spontaneous activity by 10% to 30% in 6 young guinea pig prostates (Student paired t test p<0.05). However, it had no effect on aging prostates. The cGMP analogue 8-Br-GMP (1 μM) and the PDE5 inhibitor dipyridamole (1 μM) significantly decreased the frequency of contractile activity by about 70% in 4 to 9 young and older prostates (Student paired t test p<0.05). The decrease in the response to L-NAME in spontaneous contractile and slow wave activity in aging prostate tissue compared to that in young prostates suggests that with age there is a decrease in nitric oxide production. This may further explain the increase in prostatic smooth muscle tone observed in age related prostate specific conditions, such as benign prostatic hyperplasia.

Spontaneous Ca 2+ Signaling of Interstitial Cells in the Guinea Pig Prostate

We investigated whether prostate interstitial cells generate spontaneous Ca(2+) oscillation, a proposed mechanism underlying pacemaker potentials to drive spontaneous activity in stromal smooth muscle cells. Intracellular free Ca(2+) in portions of guinea pig prostate and freshly isolated, single prostate interstitial cells were visualized using fluo-4 Ca(2+) fluorescence. Spontaneous electrical activity was recorded in situ with intracellular microelectrodes. In whole tissue preparations spontaneous Ca(2+) flashes firing synchronously across all smooth muscle cells within the field of view resulted in muscle wall contractions. Nonpropagating Ca(2+) waves were also recorded in individual smooth muscle cells. Nifedipine (Sigma®) (1 μM) largely decreased or abolished these Ca(2+) flashes and suppressed slow wave discharge upon blockade of their superimposed action potentials. Isolated prostate interstitial cells were readily distinguished from smooth muscle cells by their spiky processes and lack of contraction during intracellular Ca(2+) increases. Prostate interstitial cells generated spontaneous Ca(2+) transients in the form of whole cell flashes, intracellular Ca(2+) waves or localized Ca(2+) sparks. All 3 Ca(2+) signals were abolished by nicardipine (1 μM), cyclopiazonic acid (10 μM), caffeine (Sigma) (10 mM) or extracellular Ca(2+) removal. Prostate interstitial cells generate spontaneous Ca(2+) transients that occur at a frequency comparable to Ca(2+) flashes in situ or slow waves relying on functional internal Ca(2+) stores. However, unlike other interstitial cells in the urinary tract, Ca(2+) influx through L-type Ca(2+) channels is fundamental to Ca(2+) transient firings in prostate interstitial cells. Thus, it is not possible to conclude that prostate interstitial cells are responsible for pacemaker potential generation.

Extracellular Ca2+ entry and mobilization of inositol trisphosphate-dependent Ca2+ stores modulate histamine and electrical field stimulation induced contractions of the guinea-pig prostate

This investigation aimed to examine the source of Ca2+ mobilization that leads to the contractile response to either exogenously added histamine (1μM–1mM) or electrical field stimulation (10Hz, 0.5ms, 60V). Removal of extracellular Ca2+ by removal of Ca2+ from the bathing medium reduced histamine (1mM) induced responses by 34% and responses induced by electrical field stimulation by 94%. Similarly, blockade of L-type Ca2+ channels by nifedipine (1μM) reduced histamine (1mM) induced responses by 43% and responses induced by electrical field stimulation by 77%. Application of cyclopiazonic acid (CPA) (10μM) to inhibit Ca2+ reuptake to the sarcoplasmic reticulum enhanced both histamine-induced and electrical field stimulation induced responses to a small degree, while the addition of the inosotol triphosphate (IP3) receptor antagonist, 2-aminophenoxyethane borane (2-APB) (100μM) inhibited histamine induced responses by 70% and electrical field stimulation induced responses by 57%. Ryanodine (1μM) did not affect contractile responses to either histamine or electrical field stimulation, either in the absence or presence of 2-APB (100μM). During both histamine and electrical field stimulation induced contractions, prostate smooth muscle generates IP3 receptor mediated Ca2+ release in conjunction with Ca2+ entry from the extracellular environment. Ryanodine receptors on the other hand, appear not to play a role in this physiological mechanism.

Role of connexin 43 in the maintenance of spontaneous activity in the guinea pig prostate gland

To investigate the role of connexin 43 in the maintenance of spontaneous activity in prostate tissue from young and old guinea pigs. Conventional intracellular microelectrode and tension recording techniques, coupled with Western blot analysis and immunohistochemistry for connexin 43 (CX43) were used. The effects of three gap junction uncouplers, 18β glycyrrhetinic acid (10 µM, 40 µM), carbenoxolone (10 µM, 50 µM) and octanol (0.5 mM, 1 mM), were studied in cells displaying slow wave activity and on spontaneously contracting tissue from prostate glands of young (2-5 months) and old (9-16 months) guinea pigs. 18β Glycyrrhetinic acid (40 µM), carbenoxolone (50 µM) or octanol (0.5 mM) abolished slow wave activity in prostate tissue from young and old guinea pigs and depolarized membrane potential by approximately 5 mV. These treatments also abolished all contractions in both sets of prostate tissue. These effects were reversed upon washout. Western blot analysis and CX43 immunohistochemistry showed that there was no age-related difference in the expression and distribution of CX43 in prostate tissues. When gap junctional communication via CX43 was disrupted, spontaneous activity was abolished at a cellular and whole tissue level; CX43 is therefore essential for the maintenance of spontaneous slow wave activity and subsequent contractile activity in the guinea pig prostate gland.

Inositol trisphosphate‐dependent Ca2+ stores and mitochondria modulate slow wave activity arising from the smooth muscle cells of the guinea pig prostate gland

Changes in smooth muscle tone of the prostate gland are involved in aetiology of symptomatic prostatic hyperplasia, however the control mechanisms of prostatic smooth muscle are not well understood. Here, we have examined the role of internal Ca(2+) compartments in regulating slow wave activity in the guinea pig prostate. Standard intracellular membrane potential recording techniques were used. The majority (89%) of impaled cells displayed 'slow wave' activity. Cyclopiazonic acid (10 micromol.L(-1)) transiently depolarized (3-9 mV) the membrane potential of the prostatic stroma and transiently increased slow wave frequency. Thereafter, slow wave frequency slowly decreased over 20-30 min. Ryanodine transiently increased slow wave frequency, although after 30 min exposure slow wave frequency and time course returned to near control values. Caffeine (1 mmol.L(-1)) reduced slow wave frequency, accompanied by membrane depolarization of about 8 mV. Blockade of inositol trisphosphate receptor (IP(3)R)-mediated Ca(2+) release with 2-aminoethoxy-diphenylborate (60 micromol.L(-1)) or Xestospongin C (3 micromol.L(-1)) or inhibiting phospholipase C and IP(3) formation using U73122 (5 micromol.L(-1)) or neomycin (1 and 4 mmol.L(-1)) reduced slow wave frequency, amplitude and duration. The mitochondrial uncouplers, p-trifluoromethoxy carbonyl cyanide phenyl hydrazone (1-10 micromol.L(-1)), carbonyl cyanide m-chlorophenylhydrazone (1-3 micromol.L(-1)) or rotenone (10 micromol.L(-1)), depolarized the membrane (8-10 mV) before abolishing electrical activity. These results suggest that slow wave activity was dependent on the cyclical release of Ca(2+) from IP(3)-controlled internal stores and mitochondria. This implies that intracellular compartments were essential in the initiation and/or maintenance of the regenerative contractile activity in the guinea pig prostate gland.

α 1-adrenoceptor modulation of spontaneous electrical waveforms in the guinea-pig prostate

The aim of this study was to investigate the effects of phenylephrine on the spontaneous slow wave and pacemaker activity in the guinea-pig prostate. Membrane potential recordings were made using intracellular microelectrodes. Guinea-pig prostatic cells either displayed ‘slow wave’ activity or ‘pacemaker’ potentials. In the presence of nifedipine, none of the parameters measured were significantly different between both waveforms. Phenylephrine (1 µM) or histamine (5 µM) increased the frequency of slow waves and pacemaker potentials in the absence or presence of nifedipine (1 µM). In the presence of nifedipine (1 µM), the addition of either cyclopiazonic acid (CPA, 10 µM) or carbonyl cyanide 3-chlorophenylhydrazone (CCCP, 1–10 µM) caused an initial transient increase in frequency of the spontaneous electrical activity that was associated with a membrane depolarisation of 3–7 mV before abolishing activity. Following the cessation of electrical activity, phenylephrine (1 µM) was unable to restore the spontaneous electrical events. Although niflumic acid (10–100 µM) (in the presence of 1 µM nifedipine) similarly abolished all activity, electrical activity was promptly initiated upon the addition of phenylephrine (1 µM). These results demonstrate that in the presence of nifedipine, there are no differences between the slow waves and pacemaker potentials suggesting that both activities arise from cells that are well coupled. Both phenylephrine and histamine increased the frequency of pacemaker activity which is likely to; at least, partly explain the increase in slow wave discharge also evoked by these agents. In the presence of nifedipine, the effects observed upon α 1-adrenoceptor activation were dependent on Ca 2+ cycling by both the intracellular Ca 2+ stores and mitochondria.

Prostatic Interstitial Cells in Ageing Guinea Pig Prostates

Objective: Prostatic interstitial cells (PIC) have been previously identified in the young guinea pig and human prostates and have been suggested to be a potential new therapeutic target for diseases of the prostate gland. In this study we have established the presence of PIC and their intercellular communication via connexin 43, in the ageing guinea pig prostate. Materials and Methods: Immunohistochemical and electrophysiological techniques were used. Results: Microscopic examination of preparations of guinea pig pros-tate revealed the presence of c-Kit immunoreactive cells in the region between the smooth muscle (SM) and glandular layers in ageing guinea pigs. Connexin 43 immunoreactive cells were observed within the border between the glandu-lar layer and SM layer but not within SM layer itself. Three distinct types of electrical activity were recorded in the ageing guinea pig prostate gland: slow waves, spontaneous transient depolarisations and spike potentials. Pacemaker potentials were not recorded. Conclusion: C-Kit immuno-reactive cells are present in the ageing guinea pig prostate gland and appear to communicate to each other, but not to SM cells via connexin 43 protein. Ageing prostates do not appear to exhibit pacemaker activity, although PIC are pres-ent, indicating that the characteristics of the PIC may change with age. These results have implications in better under-standing and treating prostate-specific conditions such as benign prostatic hyperplasia.

Distribution of interstitial cells and connexin 43 in guinea-pig prostate gland

Distribution of interstitial cells and connexin 43 in guinea-pig prostate gland

Spontaneous activity in the prostate gland

We have previously reported the presence of distinct electrical activities and cell types in the guinea-pig prostate and speculated as to their functional roles. We believe that a specialised group of c-Kit immunoreactive prostatic interstitial cells (PIC) that lie between the glandular epithelium and smooth muscle stroma have a similar role to intestinal interstitial cells of Cajal (ICC), generating the pacemaker signal that manifests as slow wave activity and ensuing contractility in the smooth muscles cells of the guinea-pig prostate (1).

Spontaneous slow wave activity in aging guinea pig prostates

Spontaneous slow wave activity in aging guinea pig prostates