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Article ; Online: PDE5 inhibitors - pharmacology and clinical applications 20 years after sildenafil discovery.

Andersson, K-E

2018 Volume 175, Issue 13, Page(s) 2554–2565

Abstract: The discovery of the nitric oxide/cGMP pathway was the basis for our understanding of many normal physiological functions and the pathophysiology of several diseases. Since the discovery and introduction of sildenafil, inhibitors of PDE5 have been the ... ...

Abstract	The discovery of the nitric oxide/cGMP pathway was the basis for our understanding of many normal physiological functions and the pathophysiology of several diseases. Since the discovery and introduction of sildenafil, inhibitors of PDE5 have been the first-line therapy for erectile dysfunction (ED). The success of sildenafil in the treatment of ED stimulated research in the field of PDE5 inhibition and led to many new applications, such as treatment of lower urinary symptoms, and pulmonary arterial hypertension, which are now approved indications. However, PDE5 inhibitors have also been used in several other disorders not discussed in this review, and the fields of clinical use are increasing. In the present review, the pharmacological basis of the NO/cGMP pathway and the rationale and clinical use of PDE5 inhibitors in different diseases are discussed.
MeSH term(s)	Animals ; Cyclic GMP/antagonists & inhibitors ; Cyclic GMP/metabolism ; Drug Discovery ; Humans ; Nitric Oxide/antagonists & inhibitors ; Nitric Oxide/metabolism ; Phosphodiesterase 5 Inhibitors/pharmacology ; Sildenafil Citrate/pharmacology
Chemical Substances	Phosphodiesterase 5 Inhibitors ; Nitric Oxide (31C4KY9ESH) ; Sildenafil Citrate (BW9B0ZE037) ; Cyclic GMP (H2D2X058MU)
Language	English
Publishing date	2018-04-25
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	80081-8
ISSN	1476-5381 ; 0007-1188
ISSN (online)	1476-5381
ISSN	0007-1188
DOI	10.1111/bph.14205
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Article ; Online: Targeting neurotrophin and nitric oxide signaling to promote recovery and ameliorate neurogenic bladder dysfunction following spinal cord injury - Mechanistic concepts and clinical implications.

Kanai, A J / Andersson, K-E / Fry, C H / Yoshimura, N

Continence (Amsterdam, Netherlands)

2023 Volume 6

Abstract: This review summarizes the presentations made to a workshop entitled "Targeting Neurotrophin and Nitric Oxide Signaling to Promote Recovery and Ameliorate Neurogenic Bladder Dysfunction following Spinal Cord Injury - Mechanistic Concepts and Clinical ... ...

Abstract	This review summarizes the presentations made to a workshop entitled "Targeting Neurotrophin and Nitric Oxide Signaling to Promote Recovery and Ameliorate Neurogenic Bladder Dysfunction following Spinal Cord Injury - Mechanistic Concepts and Clinical Implications" at the International Continence Society (ICS) 2022 Vienna Meeting. Spinal cord injury (SCI; T8-T9 contusion/transection) causes impaired mobility, neurogenic detrusor overactivity (NDO), detrusor sphincter dyssynergia (DSD) and subsequent decreased quality of life. This workshop discussed the potential of future therapeutic agents that manage the lesion and its consequences, in particular possibilities to reduce the lesion itself and manage pathophysiological changes to the lower urinary tract (LUT). Attenuation of the spinal cord lesion itself was discussed with respect to the potential of a trio of agents: LM11A-3, a p75 neurotrophin receptor modulator to counter activation of local apoptotic pathways; LM22B-10 to promote neuronal growth by targeting tropomyosin-related kinase (Trk) receptors; and cinaciguat, a soluble guanylate cyclase (sGC) activator as an agent promoting angiogenesis at the injury site. The workshop also discussed targets on the bladder to block selectivity sites associated with detrusor overactivity and poor urinary filling profiles, such as purinergic pathways controlling excess contractile activity and afferent signaling, as well as excess fibrosis. Finally, the importance of increased mechanosensitive signaling as a contributor to DSD was considered, as well as potential drug targets. Overall, an emphasis was placed on targets that help restore function and reduce pathological LUT consequences, rather than downregulate normal function.
Language	English
Publishing date	2023-05-20
Publishing country	Netherlands
Document type	Journal Article
ISSN	2772-9737
ISSN (online)	2772-9737
DOI	10.1016/j.cont.2023.100703
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Article ; Online: Soluble Guanylate Cyclase Activators to Treat Benign Prostatic Hyperplasia and associated LUTS.

Kanai, A J / Andersson, K-E / Birder, L A / Fry, C H

Continence (Amsterdam, Netherlands)

2023 Volume 6

Abstract: This review summarises the presentations during a workshop session entitled "The Use of Soluble Guanylate Cyclase Activators to Treat Benign Prostatic Hyperplasia, Obstruction and Fibrosis - Mechanistic Concepts and Clinical Implications" at the ... ...

Abstract	This review summarises the presentations during a workshop session entitled "The Use of Soluble Guanylate Cyclase Activators to Treat Benign Prostatic Hyperplasia, Obstruction and Fibrosis - Mechanistic Concepts and Clinical Implications" at the International Continence Society (ICS) 2021 Melbourne Virtual meeting. Benign prostatic hyperplasia (BPH) is a highly prevalent condition that can result in bladder outflow obstruction (BOO) and development of lower urinary tract symptoms (LUTS), and by 80 years of age is present in about 75% of men. Current pharmacological therapies include
Language	English
Publishing date	2023-05-17
Publishing country	Netherlands
Document type	Journal Article
ISSN	2772-9737
ISSN (online)	2772-9737
DOI	10.1016/j.cont.2023.100699
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Article ; Online: Urethral afferent signalling: role of 5-HT paraneurons.

Andersson, K-E

Acta physiologica (Oxford, England)

2017 Volume 222, Issue 2

MeSH term(s)	Animals ; Electronic Data Processing ; Female ; Male ; Mice ; Neurons ; Serotonin ; Signal Transduction ; Urethra
Chemical Substances	Serotonin (333DO1RDJY)
Language	English
Publishing date	2017-11-28
Publishing country	England
Document type	Editorial ; Comment
ZDB-ID	2218636-0
ISSN	1748-1716 ; 1748-1708
ISSN (online)	1748-1716
ISSN	1748-1708
DOI	10.1111/apha.12993
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Article ; Online: Purinergic signalling in the urinary bladder.

Andersson, K-E

Autonomic neuroscience : basic & clinical

2015 Volume 191, Page(s) 78–81

Abstract: It is well established that in most species, exocytotic vesicular release of ATP from parasympathetic neurons contributes to contraction of the bladder. However, ATP is released not only from parasympathetic nerves, but also from the urothelium. During ... ...

Abstract	It is well established that in most species, exocytotic vesicular release of ATP from parasympathetic neurons contributes to contraction of the bladder. However, ATP is released not only from parasympathetic nerves, but also from the urothelium. During bladder filling, the urothelium is stretched and ATP is released from the umbrella cells thereby activating mechanotransduction pathways. ATP release can also be induced by various mediators present in the urine and and/or released from nerves or other components of the lamina propria. Urothelial release of ATP is mainly attributable to vesicular transport or exocytosis and, to a smaller extent, to pannexin hemichannel conductive efflux. After release, ATP acts on P2X3 and P2X2/3 receptors on suburothelial sensory nerves to initiate the voiding reflex and to mediate the sensation of bladder filling and urgency. ATP also acts on suburothelial interstitial cells/myofibroblasts generating an inward Ca(2+) transient that via gap junctions could provide a mechanism for long-distance spread of signals from the urothelium to the detrusor muscle. ATP release can be affected by urological diseases, e.g., interstitial cystitis and both the mechanisms of release and the receptors activated by ATP may be targets for future drugs for treatment of lower urinary tract disorders.
MeSH term(s)	Adenosine Triphosphate/metabolism ; Animals ; Humans ; Receptors, Purinergic/metabolism ; Urinary Bladder/metabolism
Chemical Substances	Receptors, Purinergic ; Adenosine Triphosphate (8L70Q75FXE)
Language	English
Publishing date	2015-09
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2020105-9
ISSN	1872-7484 ; 1566-0702
ISSN (online)	1872-7484
ISSN	1566-0702
DOI	10.1016/j.autneu.2015.04.012
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Article ; Online: Current and future drugs for treatment of MS-associated bladder dysfunction.

Andersson, K-E

Annals of physical and rehabilitation medicine

2014 Volume 57, Issue 5, Page(s) 321–328

Abstract: A majority of patients diagnosed with multiple sclerosis (MS) will develop lower urinary tract symptoms (LUTS) during the course of the disease. Even if antimuscarinic (anticholinergic) treatment is currently the mainstay of conservative treatment of ... ...

Abstract	A majority of patients diagnosed with multiple sclerosis (MS) will develop lower urinary tract symptoms (LUTS) during the course of the disease. Even if antimuscarinic (anticholinergic) treatment is currently the mainstay of conservative treatment of neurogenic detrusor overactivity (NDO), including MS-induced NDO, extensive data regarding their effectiveness and safeness are lacking. When antimuscarinic medications fail to prove efficacious, a further option is intradetrusor injections of onabotulinumtoxin A. In several studies, more than half (and up 76%) of the patients treated with onabotulinumtoxin A experienced significant improvement in symptoms or even achieved complete continence. Cannabis extracts have shown some promise but has still not gained wide acceptance as an effective treatment. Over the last few years many new disease-modifying drugs that have been approved and introduced for treatment of MS. These drugs may have effects not only on the MS disease process, but also on the disease symptoms, including LUTS. However, MS is not primarily a bladder disease and treatment of the underlying pathophysiology should be the main goal of treatment. Since most of the urology drugs are targeting LUTS, these drugs should be regarded as "adds on" to treatments modifying the underlying disorder. Considering that most of these drugs have not been studied specifically with respect to efficacy on LUTS, and since they are not without significant side effects, it seems important that if and when they are going to be used for treatment of bladder symptoms should be a joint decision between the neurologist and urologist taking care of the patient.
MeSH term(s)	Forecasting ; Humans ; Multiple Sclerosis/complications ; Urinary Bladder, Neurogenic/drug therapy ; Urinary Bladder, Neurogenic/etiology ; Urinary Bladder, Overactive/drug therapy ; Urinary Bladder, Overactive/etiology
Language	English
Publishing date	2014-06-02
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2480363-7
ISSN	1877-0665 ; 1877-0657
ISSN (online)	1877-0665
ISSN	1877-0657
DOI	10.1016/j.rehab.2014.05.009
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Article: Muscarinic acetylcholine receptors in the urinary tract.

Andersson, K-E

Handbook of experimental pharmacology

2011 , Issue 202, Page(s) 319–344

Abstract: Muscarinic receptors comprise five cloned subtypes, encoded by five distinct genes, which correspond to pharmacologically defined receptors (M(1)-M(5)). They belong to the family of G-protein-coupled receptors and couple differentially to the G-proteins. ...

Abstract	Muscarinic receptors comprise five cloned subtypes, encoded by five distinct genes, which correspond to pharmacologically defined receptors (M(1)-M(5)). They belong to the family of G-protein-coupled receptors and couple differentially to the G-proteins. Preferentially, the inhibitory muscarinic M(2) and M(4) receptors couple to G(i/o), whereas the excitatory muscarinic M(1), M(3), and M(5) receptors preferentially couple to G(q/11). In general, muscarinic M(1), M(3), and M(5) receptors increase intracellular calcium by mobilizing phosphoinositides that generate inositol 1,4,5-trisphosphate (InsP3) and 1,2-diacylglycerol (DAG), whereas M(2) and M(4) receptors are negatively coupled to adenylyl cyclase. Muscarinic receptors are distributed to all parts of the lower urinary tract. The clinical use of antimuscarinic drugs in the treatment of detrusor overactivity and the overactive bladder syndrome has focused interest on the muscarinic receptors not only of the detrusor, but also of other components of the bladder wall, and these have been widely studied. However, the muscarinic receptors in the urethra, prostate, and ureter, and the effects they mediate in the normal state and in different urinary tract pathologies, have so far not been well characterized. In this review, the expression of and the functional effects mediated by muscarinic receptors in the bladder, urethra, prostate, and ureters, under normal conditions and in different pathologies, are discussed.
MeSH term(s)	Acetylcholine/metabolism ; Animals ; Cholinergic Fibers/drug effects ; Cholinergic Fibers/metabolism ; Female ; Humans ; Male ; Muscarinic Agonists/therapeutic use ; Muscarinic Antagonists/therapeutic use ; Prostate/innervation ; Prostate/metabolism ; Receptors, Muscarinic/drug effects ; Receptors, Muscarinic/metabolism ; Ureter/innervation ; Ureter/metabolism ; Urethra/innervation ; Urethra/metabolism ; Urinary Bladder/innervation ; Urinary Bladder/metabolism ; Urinary Bladder, Overactive/drug therapy ; Urinary Bladder, Overactive/metabolism ; Urinary Tract/drug effects ; Urinary Tract/innervation ; Urinary Tract/metabolism
Chemical Substances	Muscarinic Agonists ; Muscarinic Antagonists ; Receptors, Muscarinic ; Acetylcholine (N9YNS0M02X)
Language	English
Publishing date	2011
Publishing country	Germany
Document type	Journal Article ; Review
ISSN	0171-2004
ISSN	0171-2004
DOI	10.1007/978-3-642-16499-6_16
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Sign. bis Bd. 125 (1997): 1982 A 2146: Show issues
danach: Sign. bei den Einzelbänden: Show issues

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Article ; Online: Mechanisms of penile erection and basis for pharmacological treatment of erectile dysfunction.

Andersson, K-E

Pharmacological reviews

2011 Volume 63, Issue 4, Page(s) 811–859

Abstract: Erection is basically a spinal reflex that can be initiated by recruitment of penile afferents, both autonomic and somatic, and supraspinal influences from visual, olfactory, and imaginary stimuli. Several central transmitters are involved in the ... ...

Abstract	Erection is basically a spinal reflex that can be initiated by recruitment of penile afferents, both autonomic and somatic, and supraspinal influences from visual, olfactory, and imaginary stimuli. Several central transmitters are involved in the erectile control. Dopamine, acetylcholine, nitric oxide (NO), and peptides, such as oxytocin and adrenocorticotropin/α-melanocyte-stimulating hormone, have a facilitatory role, whereas serotonin may be either facilitatory or inhibitory, and enkephalins are inhibitory. The balance between contractant and relaxant factors controls the degree of contraction of the smooth muscle of the corpora cavernosa (CC) and determines the functional state of the penis. Noradrenaline contracts both CC and penile vessels via stimulation of α₁-adrenoceptors. Neurogenic NO is considered the most important factor for relaxation of penile vessels and CC. The role of other mediators, released from nerves or endothelium, has not been definitely established. Erectile dysfunction (ED), defined as the "inability to achieve or maintain an erection adequate for sexual satisfaction," may have multiple causes and can be classified as psychogenic, vasculogenic or organic, neurologic, and endocrinologic. Many patients with ED respond well to the pharmacological treatments that are currently available, but there are still groups of patients in whom the response is unsatisfactory. The drugs used are able to substitute, partially or completely, the malfunctioning endogenous mechanisms that control penile erection. Most drugs have a direct action on penile tissue facilitating penile smooth muscle relaxation, including oral phosphodiesterase inhibitors and intracavernosal injections of prostaglandin E₁. Irrespective of the underlying cause, these drugs are effective in the majority of cases. Drugs with a central site of action have so far not been very successful. There is a need for therapeutic alternatives. This requires identification of new therapeutic targets and design of new approaches. Research in the field is expanding, and several promising new targets for future drugs have been identified.
MeSH term(s)	Alprostadil/pharmacology ; Alprostadil/therapeutic use ; Erectile Dysfunction/drug therapy ; Erectile Dysfunction/etiology ; Erectile Dysfunction/physiopathology ; Humans ; Male ; Nervous System Physiological Phenomena ; Neurotransmitter Agents/pharmacology ; Neurotransmitter Agents/therapeutic use ; Penile Erection/drug effects ; Penile Erection/physiology ; Phosphodiesterase Inhibitors/pharmacology ; Phosphodiesterase Inhibitors/therapeutic use
Chemical Substances	Neurotransmitter Agents ; Phosphodiesterase Inhibitors ; Alprostadil (F5TD010360)
Language	English
Publishing date	2011-12
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	209898-2
ISSN	1521-0081 ; 0031-6997
ISSN (online)	1521-0081
ISSN	0031-6997
DOI	10.1124/pr.111.004515
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Uf I Zs.148: Show issues

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Article ; Online: Urine composition in pigs is regulated in both the ureter and the bladder.

Jakobsen, L K / Andersson, K-E / Norregaard, R / Olsen, L H

Physiological research

2019 Volume 68, Issue 5, Page(s) 785–792

Abstract: The former perception of the urothelium as an impermeable barrier has been revised during the last decade, as increasing evidence of changes in urine composition during its passage of the urinary tract has been presented. Since differences in urothelial ... ...

Abstract	The former perception of the urothelium as an impermeable barrier has been revised during the last decade, as increasing evidence of changes in urine composition during its passage of the urinary tract has been presented. Since differences in urothelial permeability between upper and lower urinary tract have been found, our aim is to demonstrate whether changes in urine composition occur during passage through the ureter. We studied consecutive urine samples from both renal pelvises in six pigs and compared them to samples from the bladder and distal ureter. We further sampled urine during storage in the bladder at a fixed volume. All samples were analysed by measuring osmolality and pH, along with the concentration of the following parameters: Na(+), K(+), Cl(-), creatinine, urea. Urine alkalinity increased significantly during passage of the ureter. Creatinine concentration, pH and K(+) increased significantly during the passage from pelvis to the bladder. All other parameters increased non-significantly during the passage to the bladder. The increase in concentration was more pronounced at low concentrations in the pelvis. During storage in the bladder, there was a significant increase in urea concentration. Changes in the composition of urine occur during its passage from the renal pelvis to the bladder and during storage in the bladder. Despite the brief transit time, significant changes in alkalinity were found already during passage through the ureter.
MeSH term(s)	Animals ; Chlorides/urine ; Creatinine/urine ; Female ; Hydrogen-Ion Concentration ; Kidney Concentrating Ability ; Osmolar Concentration ; Potassium/urine ; Sodium/urine ; Sus scrofa ; Time Factors ; Urea/urine ; Ureter/metabolism ; Urinary Bladder/metabolism ; Urine/chemistry
Chemical Substances	Chlorides ; Urea (8W8T17847W) ; Sodium (9NEZ333N27) ; Creatinine (AYI8EX34EU) ; Potassium (RWP5GA015D)
Language	English
Publishing date	2019-08-19
Publishing country	Czech Republic
Document type	Comparative Study ; Journal Article
ZDB-ID	1073141-6
ISSN	1802-9973 ; 0369-9463 ; 0862-8408
ISSN (online)	1802-9973
ISSN	0369-9463 ; 0862-8408
DOI	10.33549/physiolres.934086
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Zs.A 228: Show issues

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Book: Time, space and capital

Andersson, Åke E / Andersson, David E

(New horizons in institutional and evolutionary economics)

2017

Abstract: In this challenging book, the authors demonstrate that economists tend to misunderstand capital. Frank Knight was an exception, as he argued that because all resources are more or less durable and have uncertain future uses they can consequently be ... ...

Author's details	Åke E. Andersson (Emeritus Professor of Economics, Department of Economics, Finance and Statistics, Jönköping International Business School, Jönköping, Sweden and Emeritus professor of Infrastructural Economics, Royal Institute of Technology, Stockholm, Sweden) ; David Emanuel Andersson (Senior Lecturer in Economics, Centre of Commerce and Management, RMIT University, Hanoi, Vietnam)
Series title	New horizons in institutional and evolutionary economics
Abstract	In this challenging book, the authors demonstrate that economists tend to misunderstand capital. Frank Knight was an exception, as he argued that because all resources are more or less durable and have uncertain future uses they can consequently be classed as capital. Thus, capital rather than labor is the real source of creativity, innovation, and accumulation. But capital is also a phenomenon in time and in space. Offering a new and path-breaking theory, they show how durable capital with large spatial domains - infrastructural capital such as institutions, public knowledge, and networks - can help explain the long-term development of cities and nations
Keywords	Economic development/Research ; Evolutionary economics ; Wirtschaftstheorie ; Dynamische Makroökonomie ; Kapitaltheorie ; Dynamische Wirtschaftstheorie ; Makroökonomik
Language	English
Size	vii, 304 Seiten, Illustrationen
Publisher	Edward Elgar Publishing
Publishing place	Cheltenham, UK ; Northampton, MA
Document type	Book
ISBN	9781783470877 ; 9781783470884 ; 1783470879 ; 1783470887
Database	ECONomics Information System

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