By P. Fadi. Western Montana College.

LONG-TERM POTENTIATION The idea of retrograde messengers such as NO has also been advanced with regard to hippocampal LTP (Chapter 20) generic levitra 10 mg mastercard erectile dysfunction viagra. There is a marked lack of consensus on whether NO plays a role in LTP and much discussion on why different groups find different results buy levitra 20mg lowest price erectile dysfunction see urologist. The importance of the need for a diffusible messenger in the initiation of long-term changes comes from the fact that LTP is induced by activation of postsynaptic NMDA receptors yet maintained by presynaptic changes. Thus, there is a requirement for a mediator to be generated by NMDA receptor activation and then diffuse back to the OTHER TRANSMITTERS AND MEDIATORS 285 presynaptic terminals. Unfortunately, some studies have shown that NOS inhibition blocks LTP whereas others have failed to show this. SUMMARY AND PERSPECTIVES NO differs from the more conventional NTs like the amino acids and monoamines in that it is not released from nerve terminals by arriving action potentials. It could be regarded as a second messenger except that its effects appear to be mediated by the production of cGMP, itself an established second messenger. The fact that its synthesis and release from neurons, and so its actions, are dependent on and stimulated by Ca2‡ influx, often after NMDA receptor activation, inevitably links NO to more extreme excitatory effects such as LTP, excitotoxicity, pain and possibly also epilepsy. Whether blocking its synthesis will be a more effective therapeutic approach than the use of NMDA receptor antagonists is problematic in that even if really specific NOS inhibitors are developed these effects will potentially be at least as widespread as block of NMDA receptors. Where NO inhibition may have the advantage is that it should only operate under conditions of NMDA action that are above normal and so may only affect adverse but not normal neuronal function. This should only occur in those brain areas and pathways showing that extreme level of activity. REFERENCES AND FURTHER READING Ash, ASF and Schild, HO (1966) Receptors mediating some actions of histamine. Bardoni, R, Goldstein, PA, Justin Lee, C, Gee, JG and MacDermott, AB (1997) ATP P2x receptors mediate fast synaptic transmission in the dorsal horn of the rat spinal cord. Baulieu, EE (1997) Neurosteroids: of the nervous system, by the nervous system, for the nervous system. Black, JW, Duncan, WAM, Durant, CJ, Ganellin, CR and Parsons, ME (1972) Definition and antagonism of histamine H2 receptors. Boulton, AA, Baker, GB, Dewhurst, NG and Sandller, M (Eds) (1984) Neurobiology of the Trace Amines, Humana Press, Totowa, NJ. Bredt, DS and Synder, SH (1994) Nitric oxide: a physiologic messenger molecule. Burnstock, G, Campbell, G, Satchell, D and Smythe, A (1970) Evidence that adenosine triphosphate or a related nucleotide is the transmitter substance released by non-adrenergic inhibitory nerves in the gut. Cox, B, Lee, TF and Martin, D (1981) Different hypothalamic receptors mediate 5-hydroxy- tryptamine and tryptamine induced core temperative changes in the rat. Dumuis, A, Sebben, M, Haynes, L, Pin, JP and Bockaert, J (1988) NMDA receptors activate the arachidonic acid cascade system in striatal neurons. Edwards, FA, Gibb, AJ and Colquhoun, D (1992) ATP receptor mediated synaptic currents in the central nervous system. Gasior, M, Carter, RB and Witkin, JM (1999) Neuroactive steroids: potential therapeutic use in neurological and psychiatric disorders. Grahame-Smith, DG (1971) Studies in vivo on the relationship between brain tryptophan, brain 5HT synthesis and hyperactivity in rats treated with a monoamine oxidase inhibitor and L- tryptophan. Greene, RN and Haas, HL (1991) The electrophysiology of adenosine in the mammalian central nervous system. Griffith, O and Stuehr, D (1995) NO synathases: properties and catalytic mechanisms. Harrison, NL and Simmonds, MA (1984) Modulation of the GABA receptor complex by a steroid anaesthetic. Henbockel, T and Pap, HC (1999) Modulatory effects of adenosine on inhibitory postsynaptic potentials in the lateral amygdala of the rat. Hough, LS and Green, JP (1983) Histamine and its receptors in the nervous system. Jacobsen, KA (1998) Adenosine A3 receptors: novel ligands and paradoxical effects. Jones, RSG (1983) Trace biogenic amines: a possible functional role in the CNS. Koenig, HL, Schumacher, M, Ferzaz, B, DeThi, A, Ressouches, A, Gennoun, R, Jung-Tester, L, Robel, P, Akwa, Y and Baulieu, EE (1995) Progesterone synthesis and myelin formation by Schwann cells. Leurs, R, Blandina, P, Tedford, C and Timmerman, H (1998) Therapeutic potential of histamine H3 receptor agonists and antagonists.

In females purchase 10 mg levitra amex erectile dysfunction gluten, the urinary bladder is in contact with the uterus and vagina 20 mg levitra free shipping impotence essential oils. The shape of the urinary bladder is determined by the vol- ume of urine it contains. An empty urinary bladder is pyramidal; as it fills, it becomes ovoid and bulges upward into the abdominal cavity. The median umbilical ligament, a fibrous remnant of the embryonic urachus (see Developmental Exposition, pp. The base of the urinary bladder receives the ureters, and the urethra exits at the inferior angle, or apex. The region surrounding the urethral opening is known as the neck of the urinary bladder. The internal trigone lacks rugae; it is therefore smooth in appearance and remains rel- atively fixed in position as the urinary bladder changes shape trigone: L. Urinary System © The McGraw−Hill Anatomy, Sixth Edition Body Companies, 2001 686 Unit 6 Maintenance of the Body Urinary bladder Urinary bladder Urethra Prostatic part of urethra Membranous part of urethra Bulbourethral gland (b) Corpus cavernosum penis Spongy part of urethra (a) FIGURE 19. It consists of a prostatic part that passes through the prostate, a membranous part that passes through the urogenital diaphragm, and a spongy part that passes through the penis. Urinary System © The McGraw−Hill Anatomy, Sixth Edition Body Companies, 2001 Chapter 19 Urinary System 687 The second layer of the urinary bladder, the submucosa, The urethra of the male serves both the urinary and repro- functions to support the mucosa. At the neck of the urinary bladder, can be identified in the male urethra: the prostatic part, the the detrusor muscle is modified to form the superior (called the membranous part, and the spongy part (fig. It appears only on the superior surface of the urinary the neck of the urinary bladder. The portion of the urethra re- bladder and is actually a continuation of the parietal peritoneum. The external urethral sphincter muscle The autonomic nerves serving the urinary bladder are de- is located in this portion. Sympathetic innervation arises from The spongy part of the urethra is the longest portion (15 the last thoracic and first and second lumbar spinal nerves to cm), extending from the outer edge of the urogenital diaphragm serve the trigone, urethral openings, and blood vessels of the uri- to the external urethral orifice on the glans penis. Parasympathetic innervation arises from the sec- surrounded by erectile tissue as it passes through the corpus spon- ond, third, and fourth sacral nerves to serve the detrusor muscle. The ducts of the bulbourethral glands (Cow- The sensory receptors of the urinary bladder respond to disten- per’s glands) of the reproductive system attach to the spongy part sion and relay impulses to the central nervous system via the of the urethra near the urogenital diaphragm. The urinary bladder becomes infected easily, and because a woman’s urethra is so much shorter than a man’s, women are Micturition particularly susceptible to urinary bladder infections. It is a infection that involves the renal pelvis is called pyelitis; if it continues complex function that requires a stimulus from the urinary blad- into the nephrons, it is known as pyelonephritis. To reduce the risk of der and a combination of involuntary and voluntary nerve im- these infections, a young girl should be taught to wipe her anal re- gion in a posterior direction, away from the urethral orifice, after a pulses to the appropriate muscular structures of the urinary bowel movement. In young children, micturition is a simple reflex action that occurs when the urinary bladder becomes sufficiently distended. Urethra Voluntary control of micturition is normally developed by the time a child is 2 or 3 years old. Specialized urethral glands, embedded in average capacity of the urinary bladder is 700 to 800 ml. A vol- the urethral wall, secrete protective mucus into the urethral canal. The invol- stimulate stretch receptors and trigger the micturition reflex, cre- untary smooth muscle sphincter, the superior of the two, is the ating a desire to urinate. The lower sphincter, composed of third, and fourth sacral segments of the spinal cord. Following voluntary skeletal muscle fibers, is called the external urethral stimulation of this center by impulses arising from stretch recep- sphincter (fig. Stimulation of these muscles causes a rhythmic contrac- fice into the vestibule between the labia minora. The urethral tion of the urinary bladder wall and a relaxation of the internal orifice is positioned between the clitoris and vaginal orifice (see urethral sphincter. The female urethra has a single function: to transport ceived in the brain, but there is still voluntary control over urine to the exterior. Urinary System © The McGraw−Hill Anatomy, Sixth Edition Body Companies, 2001 688 Unit 6 Maintenance of the Body FIGURE 19.

Blows to the head cornea that can be associated with a num- or the eye can also cause damage to the ber of infectious conditions buy 20 mg levitra visa prostate cancer erectile dysfunction statistics, including her- internal structures of the eye purchase levitra 20mg on line erectile dysfunction due to diabetes icd 9, causing pes simplex (herpetic keratitis); it can also hemorrhage, retinal damage, or other be a complication of HIV. Microb- intraocular pressure, surgical intervention ial keratitis is associated with the use of may be needed to relieve the pressure and contact lenses and is usually caused by im- prevent further damage. One decreases the physician who specializes in diseases and risk of infection by washing hands and treatment of the eye). The degree of visu- using the appropriate technique for clean- al loss that results from an eye injury is a ing and applying contact lenses. Using Glaucoma is a condition involving in- appropriate eye protection for work, creased intraocular pressure. If left untreat- home, and sports activities that carry a risk ed, permanent damage to the optic nerve of eye injury is one of the major forms of can result, causing blindness. Glaucoma The most common eye disease is con- occurs when the amount of aqueous junctivitis (inflammation of the mem- humor produced exceeds the amount brane that lines the eye, the conjunctiva. In most instances, even though the drainage pipe is blocked, conjunctivitis is easily treated, is self-lim- resulting in overaccumulation of water in iting, and has no permanent effects. Some types of infectious conjunctivitis, such as gonococcal conjunctivitis, or tra- Types of Glaucoma choma, however, can cause ulceration of the cornea and subsequent blindness. Uveitis is an inflammation of the uveal Broad categories are based on the reason tract (iris, ciliary body, choroid). Because the outflow no longer equals the inflow, the amount of Treatment of glaucoma is directed to- aqueous humor builds and pressure in the ward reducing the intraocular pressure by eye increases. Open-angle glaucoma gen- decreasing the amount of aqueous humor erally progresses slowly over many years, produced or by increasing its outflow. This producing no symptoms until the optic can be accomplished with medication or nerve is sufficiently damaged to reduce through surgically creating a new pathway visual acuity and visual field. Vision loss gen- Medication for the treatment of glauco- erally begins with the loss of peripheral ma, whether eye drops or oral medication, (side) vision so that individuals can see must be used daily throughout life to con- only straight ahead, as if looking through trol eye pressure and prevent further dam- a tunnel (tunnel vision). In either type of glaucoma, peripheral vision is often gradual, individ- early detection and treatment are critical uals may be unaware of the problem until to prevent irreversible damage to the optic advanced stages of the condition. Regard- treated, the field of vision continues to less of the type of glaucoma, lifetime med- narrow until all vision is lost. Treatment of Chronic Acute Closed-Angle Glaucoma Open-Angle Glaucoma Acute closed-angle glaucoma develops Chronic open-angle glaucoma may be much more rapidly than chronic open- controlled with medication in the form of angle glaucoma and is a medical emer- eye drops alone to decrease production of gency. Symptoms include sudden severe aqueous humor or in combination with pain, sharply decreased vision, nausea and oral medication that reduces pressure in vomiting, and rapid damage to the optic the eye, thus halting progression of the nerve with associated vision loss. Because eye drops are absorbed closed-angle glaucoma results from an into the bloodstream, they may affect oth- abrupt blockage and obstruction of the er body functions and cause systemic side canal of Schlemm so that aqueous humor effects ranging from generalized weakness rapidly accumulates in the anterior to central nervous system, cardiovascular, chamber of the eye. Oral med- angle glaucoma is much less common ications for the treatment of glaucoma than chronic open-angle glaucoma, it is work by decreasing the production of a medical emergency and must be treat- aqueous humor. For example, arteriosclerot- medical supervision, not only to monitor ic retinopathy is due to changes that occur the condition itself but also to identify any in blood vessels in the retina because of side effects of the medication. Hypertensive retinopathy is When intraocular pressure cannot be due to changes that occur in blood vessels successfully controlled with medication, in the retina because of high blood pres- individuals with chronic open-angle glau- sure. In both instances, treatment of the coma may have a surgical procedure primary underlying condition can control called trabeculectomy that relieves pressure the progress of retinopathy. Individuals may also need and the most common cause of blindness, to continue using eye drops or oral med- is diabetic retinopathy. Diabetic retinopathy ication after surgery to control pressure; is the result of damage to the retina and is however, in some instances surgery may a complication of diabetes mellitus (see eliminate the need for medication. Treatment of Acute Closed-Angle Glaucoma Consequently, regular comprehensive eye examinations by a physician are impor- Acute closed-angle glaucoma results tant in helping to prevent visual loss. Nonproliferative diabetic retinopathy miotics constrict the pupil, thus enlarging 2. Proliferative diabetic retinopathy the drainage passageway and facilitating the outflow of aqueous humor. Because of Nonproliferative diabetic retinopathy is the emergency nature of acute closed- caused by changes in blood vessel walls angle glaucoma, oral or intravenous med- that allow fluids to leak into retinal tissue. As a rior chamber of the eye, thus preventing result, retinal tissues receive too little oxy- further eye damage by relieving built-up gen (ischemia) and growth of new vessels pressure. At times iridotomy abnormally fragile and prone to bleed, may also be performed prophylactically in causing hemorrhage into the vitreous the unaffected eye after an acute attack. Vessels Retinopathy may burst, filling the back of the eye with blood and resulting in significant visual Any disease or disorder of the retina is loss.

Jacobs order levitra 20 mg overnight delivery erectile dysfunction only with partner, BL and Fornal purchase 20mg levitra erectile dysfunction pump walgreens, CA (1999) Activity of serotonergic neurons in behaving animals. Krebs-Thomson, K, Paulus, MP and Geyer, MA (1998) Effects of hallucinogens on locomotor and investigatory activity and patterns: influence of 5-HT2A and 5-HT2C receptors. Leibowitz, SF, Alexander, JT (1998) Hypothalamic serotonin in control of eating behavior, meal size, and body weight. Lowry, CA, Odda, JE, Lightman, SL and Ingram, CD (2000) Corticotropin-releasing factor (CRF) increases the in vitro firing rates of serotonergic neurones in the rat dorsal raphe nucleus: evidence for selective activation of a topographically organised mesolimbocortical system. Massot, O, Rousselle, JC, Grimaldi, B, Cloez-Tayarani, I, Fillion, MP, Plantefol, M, Bonnin, A, Prudhomme, N and Fillion, G (1998) Molecular, cellular and physiological characteristics of 5-HYDROXYTRYPTAMINE 209 5-HT-moduline, a novel endogenous modulator of 5-HT1B receptor subtype. McQueen, JK, Wilson, H, Sumner, BEH and Fink, G (1999) Serotonin transporter (SERT) mRNA and binding site densities in male rat brain affected by sex steroids. Petty, F, Kramer, G, Wilson, L and Jordan, S (1994) In vivo serotonin release and learned helplessness. Petty, F, Jordan, S, Kramer, GL, Zukas, PK and Wu, J (1997) Benzodiazepine prevention of swim-stress induced sensitization of cortical biogenic amines: an in vivo microdialysis study. Povlock, SL and Amara, SG (1997) The structure and function of norepinephrine, dopamine and serotonin transporters. Ramamoorthy, S and Blakely, RD (1999) Phosphorylation and sequestration of serotonin transporters differentially modulated by psychostimulants. Rouch, C, Nicolaidis, S and Orosco, M (1999) Determination, using microdialysis, of hypothalamic serotonin variations in response to different macronutrients. Rudnick, G (1997) Mechanism of biogenic amine neurotransmitter transporters. Samanin, R and Grignaschi, G (1996) Role of 5-hydroxytryptamine receptor subtypes in satiety and animal models of eating disorders. In Drug Receptor Subtypes and Ingestive Behaviour (Eds Cooper, SJ and Clifton, PG), Academic Press, London, pp. Siuciak, JA, Clark, MS, Rind, HB, Whittemore, SR and Russo, AF (1998) BDNF induction of tryptophan hydroxylase mRNA levels in the rat brain. Sprague, JE, Everman, SL and Nichols, DE (1998) An integrated hypothesis for the serotonergic axonal loss induced by 3,4-methylenedioxymethamphetamine. Stock, MJ (1997) Sibutramine: a review of the pharmacology of a novel anti-obesity agent. Takahashi, H, Takada, Y, Nagai, N, Urano, T and Takada, A (1998) Extracellular serotonin in the striatum is increased after immobilisation stress only in the nighttime. Uphouse, L (1997) Multiple serotonin receptors: too many, not enough, or just the right number? Boutelle, MG and Fillenz, M (1995) Effects of changes in rat brain glucose on serotonergic and noradrenergic neurons. Wurtman, RJ and Wurtman, JJ (1995) Brain serotonin, carbohydrate-craving, obesity and depression. Yoshioka, M, Matsumoto, M, Togashi, H and Saito, H (1995) Effects of conditioned fear stress on 5-HT release in the rat prefrontal cortex. Edited by Roy Webster Copyright & 2001 John Wiley & Sons Ltd ISBN: Hardback 0-471-97819-1 Paperback 0-471-98586-4 Electronic 0-470-84657-7 10 ino cids: Excitatory A. In fact,of the billions of long-axon neurons in the central nervous system,the majority use glutamate as their principal transmitter as do excitatory intrinsic neurons. A large proportion of peripheral sensory fibres conveying touch- and pain-related information contain glutamate and aspartate as do visual, auditory and other sensory afferent fibres. This is also the case for neurons in the CNS linking different areas of the brain and spinal cord. Due to the metabolic role of glutamate and the fact that it is the precursor for GABA,the inhibitory amino-acid, precise localisation studies have been fraught with difficulties. However,both release studies and,more importantly,electrophysiological recordings have shown that glutamate functions as a transmitter at many synapses. In the case of C-fibres,the co-existence of glutamate with peptides such as substance P and/or CGRP would make it highly likely that a noxious stimulus releases both peptides and excitatory amino acids from the afferent nociceptive fibres.

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