1 Sodium hydrogen sulphide (NaHS), a donor of hydrogen sulphide (H 2 S), produced dose-related relaxation of the rabbit isolated ileum (EC 50 , 76.4+7.9 mM) and rat vas deferens (EC 50 , 64.8+5.4 mM) and reduced ACh-mediated contraction of the guinea-pig isolated ileum. 2 NaHS also reduced the response of the guinea-pig (EC 50 , 80.0+5.7 mM) and rat (EC 50 , 108.2+11.2 mM) ileum preparations to electrical stimulation of the intramural nerves. In guinea-pig ileum this e ect was spontaneously reversible and mimicked by sodium nitroprusside (SNP, EC 50 , 2.1 mM). Combination of NaHS (20 mM) with SNP (0.5 mM) produced a greater than additive inhibition of the twitch response of the ileum to electrical stimulation. 3 The inhibitory e ect of NaHS on the ®eld-stimulated guinea-pig ileum was una ected by pretreatment with L-NAME (100 mM), indomethacin (10 mM), naloxone (1 mM) or glibenclamide (100 mM). Furthermore, NaHS (200 mM) did not a ect the contractile response of the ileum to KCl (10 to 60 mM). 4 Propargylglycine (PAG, 1 mM) and b-cyanoalanine (BCA, 1 mM) (inhibitors of cystathionine-glyase) but not aminooxyacetic acid (AOAA, 1 mM) (inhibitor of cystathionine-b-synthetase) caused a slowly developing increase in the contraction of the guinea-pig ileum to ®eld stimulation. This e ect was reversed by cysteine (1 mM). 5 These results show that NaHS relaxes gastrointestinal and urogenital smooth muscle and suggest that H 2 S is responsible for these e ects. The possibility that endogenous H 2 S, formed as a consequence of activation of intramural nerves, plays a part in controlling the contractility of the guinea-pig ileum is discussed.

Sphingosylphosphorylcholine (SPC) is a powerful vasoconstrictor, but in vitro its EC(50) is approximately 100-fold more than plasma concentrations. We examined whether subcontractile concentrations of SPC (100 nmol/L of SPC, and independent of the endothelium, 2-aminoethoxydiphenylborane-sensitive Ca(2+) entry, and Rho kinase. It was abolished by the phospholipase C inhibitor U73122, the broad spectrum protein kinase C (PKC) inhibitor Ro31-8220, and the PKC delta inhibitor rottlerin, but not by Gö6976, which is ineffective against PKC delta. The potentiation could be attributed to enhancement of Ca(2+) entry. SPC also potentiated the responses to prostaglandin F(2 alpha) and U436619, which activate a 2-aminoethoxydiphenylborane sensitive nonselective cation channel in intrapulmonary arteries. In this case, potentiation was partially inhibited by diltiazem but abolished by 2-aminoethoxydiphenylborane, Ro31-8220, and rottlerin. SPC (1 micromol/L) caused translocation of PKC delta to the perinuclear region and cytoskeleton of cultured intrapulmonary artery smooth muscle cells. We present the novel finding that low, subcontractile concentrations of SPC potentiate Ca(2+) entry in intrapulmonary arteries through both voltage-dependent and independent pathways via a receptor-dependent mechanism involving PKC delta. This has implications for the physiological role of SPC, especially in cardiovascular disease, where SPC is reported to be elevated.

Purpose This paper aims to highlight the critical importance of the perspectives of mental health service-users during the COVID-19 pandemic. Design/methodology/approach This viewpoint is based on a review of recent research and literature and draws on consultations with experts by experience, including the lead author. Findings The authors argue that expertise-by-experience is critical to policy, service development and research; but there is a risk it will be neglected at a time of rapid and reactive clinical development. Research limitations/implications Understanding and responding to the nuances of individual need can only be achieved through coproducing service strategy design, delivery and research with mental health service users. The consultation outlined in this viewpoint gives some indication of the type of valuable insights that can be gained through seeking and listening to the perspectives of experts by experience. Originality/value The discussions revealed that experience of managing severe and complex mental health conditions can actually be advantageous when facing a crisis such as COVID-19.