The aim of this study was to test the hypothesis that Huntington's disease is associated with impaired phospholipid-related signal transduction using the niacin skin flush test. This is the first reported use of this test in this patient group. The response to topical aqueous methyl nicotinate solution was recorded at 5 min intervals over 20 min in six in-patients with advanced (stage III) Huntington's disease and in 14 age- and sex-matched normal individuals with no history of this or any other major neurological disorder. The volumetric niacin response (VNR) (mean ± S.E.M.) in the patients with Huntington's disease, 16.3 ± 2.6 mol s l-1, was significantly lower than the mean VNR of 28.3 ± 2.1 mol s l-1 in the control group (P = 0.004). These results are consistent with the conclusion that Huntington's disease may be associated with an abnormality of neuronal membrane fatty acid metabolism, possibly as a consequence of an as yet unidentified action of huntingtin. Experimental Physiology (2001) 86.5, 683-685.

Preterm delivery is the largest cause of perinatal mortality and morbidity, yet the treatment of preterm labour has not been demonstrated to improve outcome. The reasons are numerous and complex, but they include a failure to understand the mechanism(s) of preterm labour, the multitude of different causes, the difficulty in diagnosis and the problems of outcome measurement in clinical trials. Recently, an oxytocin antagonist (atosiban) has been introduced into clinical practice in Europe. Although it may be an effective tocolytic, a beneficial effect on perinatal outcome has not been demonstrated. Atosiban has an effect at both oxytocin and vasopressin (V1a) receptors, which (assuming efficacy) raises the question as to whether oxytocin or vasopressin V1a antagonism is required for tocolysis. This review examines the rationale for tocolysis in preterm labour, the evidence for administration of atosiban and the role for oxytocin, vasopressin and their receptors in the onset of labour. Experimental Physiology (2001) 86.2, 297-302.

Nitric Oxide and the Peripheral Nervous System. Edited by N. TODA, S. MONCADA, R. FURCHGOTT and E. A. HIGGS. Pp. 200. Portland Press Ltd, 2000. £85.00 hardback. ISBN 1 85578 139 5.

This is a timely text that provides an overview of the role of nitric oxide (NO) in the peripheral nervous system (PNS). The volume consists of ten chapters. The main focus is on the distribution of neuronal NOS in various nitrergic systems, and the role played by NO as a paracrine and autocrine agent in various physiological and pathophysiological states. Specifically, chapter 1 provides a thorough review of the basic histochemistry of NO in the PNS. The molecular biology of NOS and the use of NOS knockout models to study physiological function are well illustrated in chapter 2. What is not stressed is that different isoforms of NOS may sit in other cell types besides the tissue specific site suggested by the name of the isoform, and that as well as producing NO, superoxide anions may also be generated, thereby potentially complicating interpretation of data. Chapter 3 paints an important role for nitrergic nerves in the control of vascular tone, although there is no mention of the role played by NO in hypoxic and hypercapnia regulation of the peripheral circulation or its role in the peripheral autonomic control of cardiac excitability. The latter area is now a large field and certainly warranted a stand-alone chapter.

The chapters (4 and 5) on non-adrenergic non-cholinergic (NANC) nerves involved in neurotransmission in the urogenital tract demonstrate one of the best examples of nitrergic neurotransmission, e.g. penile erection. There are also good sections on the pathophysiological basis of male erectile dysfunction and interesting speculations for future direction. A detailed anatomical description of nitric oxide synthase (NOS)-containing tissue in the lower urinary tract is also given. Of interest, impaired L-arginine-NO-cGMP pathway leads to impaired relaxation of the outflow region, bladder hypertrophy, and increased afferent activity and bladder hyperactivity. In the respiratory tract (chapter 6) NO is not seen as a classical transmitter; however, it may play a role in modulating autonomic neurotransmission as has been recently demonstrated in the heart. There is clearer evidence in chapter 7 that NO acts as an enteric inhibitory neurotransmitter. The final three chapters deal with neurogenic NO and exocrine secretion in the gastrointestinal (GI) tract (chapter 8), spinal pain processing (chapter 9) and neurogenic inflammation (chapter 10). These chapters present important information that may point to potential therapeutic targets and are well written.

Overall this book is worth purchasing, albeit with a few omissions and understatements, although most chapters are first class in all respects. Experimental Physiology (2001) 86.5, 687.

G-protein coupled receptors (GPCRs) are key to maintaining uterine quiescence and inducing phasic contractions at term. However, the biochemical mechanisms whereby uterine GPCRs are desensitised and re-sensitised during these physiological conditions are unknown. For example, the number of oxytocin receptors (OTRs) on uterine myocytes decrease significantly after the addition of oxytocin. Therefore, further understanding of the desensitisation/re-sensitisation of the OTR and other uterine GPCRs during pregnancy may provide a target for more efficient tocolytic drugs and more selective ways to modulate uterine activity. Here, we briefly review some of the mechanisms that may be involved during OTR and other GPCR desensitisation. Experimental Physiology (2001) 86.2, 303-312.

Myosin light chain kinase (MLCK) is essential for myometrial contractions induced by calcium-mobilizing agonists. From the gene of vertebrate smooth muscle/non-muscle MLCK there are at least four proteins expressed. We have found that both a > 200 and a 137 kDa MLCK are equally expressed in human non-pregnant (NP) and term pregnant (P) uterine smooth muscle and confirmed that 19 kDa telokin (TK) is only expressed in P myometrium. In addition, we have observed that a MLCK immunogen at ~60 kDa is only expressed in NP myometrium, suggesting that its expression is inhibited during normal pregnancy in a hormonally dependent manner. However, when we compared pregnant myometrium from patients delivered preterm (PT) (< 34 weeks gestation), but not in labour (NIL), with PT patients in labour (IL) we found that PT(IL) samples expressed the ~ 60 kDa MLCK immunogen and thus displayed a NP phenotype whereas PT(NIL) samples did not express the protein and retained a pregnant phenotype. We hypothesize that the novel ~ 60 kDa MLCK immunogen contributes to the aberrent contractility associated with preterm labour. Experimental Physiology (2001) 86.2, 313-318.