Effects of substance P on inositol triphosphate accumulation, on contractile responses and on arachidonic acid release and prostaglandin biosynthesis in rabbit iris sphincter muscle

Yousufzai, Sardar Y.K.; Akhtar, Rashid A.; Abdel‐Latif, Ata A.

doi:10.1016/s0014-4835(86)80089-6

Cited by 32 publications

(11 citation statements)

References 25 publications

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“…Furthermore, activation of the NK 1 receptor has been shown to work via the inositol triphosphate (IP 3 ) second messenger system, which serves to increase the intracellular concentration of Ca 2+ (Krause et al 1990; Regoli et al 1994; Mann et al 1999). The production of NO via NO synthase is a Ca 2+ ‐dependent mechanism, and the production of prostaglandins has been shown to rely, at least in part, on an increase in intracellular Ca 2+ and IP 3 (Yousufzai et al 1986; Marriott et al 1991). However, data from the present study suggest NK 1 receptor activation may only account for a portion of the NO component.…”

Section: Discussionmentioning

confidence: 99%

Neurokinin‐1 receptor desensitization attenuates cutaneous active vasodilatation in humans

Wong

Minson

2006

The Journal of Physiology

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To date, the neurotransmitter(s) and pathways involved in cutaneous active vasodilatation are not fully understood. The purpose of this study was to determine the potential involvement of neurokinin-1 (NK 1 ) receptors to active vasodilatation. Our experimental model exploited our previous findings that repeated microdialysis infusions of substance P desensitize the NK 1 receptors and that substance P-induced vasodilatation contains a substantial nitric oxide (NO) component. Eleven subjects were equipped with four microdialysis fibres on the ventral forearm. Site 1 served as a control and received a continuous infusion of Ringer solution. Site 2 received a continuous infusion of 10 mM L-NAME to inhibit NO synthase. Site 3 received a 10 μM dose of substance P to desensitize the NK 1 receptors prior to whole-body heating. Site 4 received a 10 μM dose of substance P combined with 10 mM L-NAME. Red blood cell (RBC) flux was measured via laser-Doppler flowmetry, and cutaneous vascular conductance (CVC) was calculated as RBC flux/mean arterial pressure and normalized to maximal vasodilatation via 28 mM sodium nitroprusside. Substance P was infused for 15 min at 4 μl min −1 in sites 3 and 4, and skin blood flow was allowed to return to baseline (∼45-60 min). Subjects then underwent a period of whole-body heat stress to raise oral temperature 0.8-1.0• C above baseline. Pretreatment with substance P increased CVC to 48 ± 2% CVC max , which was significantly greater than for sites pretreated with substance P combined with L-NAME (27 ± 2% CVC max ; P < 0.001). During whole-body heating, CVC in control sites increased to 69 ± 3% CVC max . Sites pretreated with substance P (48 ± 3% CVC max ) were significantly reduced compared to control sites (P < 0.001). The CVC response to whole-body heat stress in L-NAME sites was significantly reduced (32 ± 3% CVC max ; P < 0.001) compared to both control sites and sites pretreated with substance P. The CVC response to whole-body heating was nearly abolished in sites pretreated with substance P combined with L-NAME (20 ± 2% CVC max ) and was significantly reduced compared to the other three sites (all P < 0.001). These data suggest NK 1 receptors contribute to active vasodilatation and that combined NK 1 receptor desensitization and NO synthase inhibition further diminishes active vasodilatation.

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Section: Discussionmentioning

confidence: 99%

Neurokinin‐1 receptor desensitization attenuates cutaneous active vasodilatation in humans

Wong

Minson

2006

The Journal of Physiology

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“…Substance P stimulates phosphatidyl inositol hydrolysis in smooth muscle (Watson & Downes, 1983;Yousufzai et al, 1986) and paratoid acinar cells (Aub & Putney, 1984), and is likely to act in a similar manner in endothelial cells. Thus, if all three agonists act by increasing phosphatidyl inositol hydrolysis (proven for bradykinin and ATP, assumed for substance P), but PDB only inhibits EDRF release induced by substance P and ATP, one must question whether the mechanism of action of PDB acting via protein kinase C, is through inhibition of the phospholipase C enzyme per se.…”

Section: Discussionmentioning

confidence: 99%

Release of endothelium‐derived relaxing factor from pig cultured aortic endothelial cells, as assessed by changes in endothelial cell cyclic GMP content, is inhibited by a phorbol ester

Smith

Lang

1990

British J Pharmacology

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Cultured aortic endothelial cells of the pig respond to the endothelium‐derived relaxing factor (EDRF) they release with an increase in cyclic GMP content. This response is inhibited by haemoglobin or by l‐NG‐monomethyl‐arginine (l‐NMMA), and has been used to investigate the effects of phorbol esters on EDRF release. Pretreatment with phorbol‐12,13‐dibutyrate (PDB) but not the inactive 4α‐phorbol‐12,13,‐didecanoate (PDD), inhibited increases in cyclic GMP induced by substance P (10−8 m) in a time and concentration‐dependent manner. PDB did not affect basal cyclic GMP levels. PDB (3 × 10−7 m), but not PDD (3 × 10−7 m), also inhibited ATP (10−5 m)‐induced increases in cyclic GMP, but did not affect those induced by bradykinin (10−7 m). Increases in cyclic GMP induced by low (10−7 m) but not high (10−6 m) concentrations of the calcium ionophore A23187 were inhibited by PDB (3 × 10−7 m). This inhibitory effect was due to enhanced destruction of EDRF by superoxide anions rather than inhibition of EDRF release, as the inhibition was abolished in the presence of superoxide dismutase (SOD, 30 u ml−1) and catalase (CAT, 100 u ml−1). SOD and CAT did not affect the inhibitory action of PDB on substance P or ATP‐induced increases in cyclic GMP. Increases in endothelial cell cyclic GMP content induced by sodium nitroprusside (10−5 m) were unaffected by PDB pretreatment. The inhibitory effects of PDB are probably a result of an action of protein kinase C on the steps between receptor occupation and phospholipase C activation.

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“…Firstly, SP may stimulate prostaglandin release which, in turn, activates the postsynaptic neuron. A SP induction of prostaglandin release has been reported from, for example, macrophages (Hartung, Wolters & Toyka, 1986) and muscle cells (Yousufzai, Akhtar & Abdel-Latif, 1986). Furthermore, PGE2 has been shown to cause intestinal secretion via nerves in the cat jejunum in vivo (Brunsson, Sjoqvist, Jodal & Lundgren, 1987) and in rat colon descendens in vitro (Diener, Bridges, Knobloch & Rummel, 1988).…”

Section: Methodsmentioning

confidence: 95%

Substance P effects on blood flow, fluid transport and vasoactive intestinal polypeptide release in the feline small intestine.

Brunsson

Fahrenkrug

Jodal

et al. 1995

The Journal of Physiology

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1. Substance P (SP) infusions were given close I.A. to the feline small intestine in vivo in a dose that produced plasma concentrations of 1-5 /AM. This infusion regularly evoked a net fluid secretion measured with a gravimetric technique. Concomitantly, the release into blood of vasoactive intestinal polypeptide (VIP), a putative neurotransmitter of the enteric nervous system, increased. 2. The SP-induced fluid secretion was blocked by tetrodotoxin (7 ,ug close I.A.), a blocker of fast sodium channels in excitable tissues, and hexamethonium (10 mg (kg body wt)-', i.v.), a nicotinic receptor antagonist, suggesting that the SP effect was mediated by the enteric nervous system. In line with this it was shown that the SP-evoked release of VIP was also significantly diminished by hexamethonium. secretion caused by SP, indicating that the effects of SP were not due to the actions of prostaglandins or histamine. 5. It is proposed that SP activates a nervous reflex arch that we have shown to be activated by various luminal stimuli, including cholera toxin. The proposed reflex is made up of at least three neurons: an afferent neuron going from the mucosa to the myenteric plexus, a cholinergic interneuron and a VIP-ergic neuron from the submucosal plexus controlling the enterocytes. Met-enkephalin and the sympathetic nerves decrease the fluid secretion by pre-or postsynaptic inhibition of reflex nervous activity.We have previously shown in cat and rat experiments that the fluid secretion evoked by placing cholera toxin in the intestinal lumen or by exposing the intestinal serosa to hydrochloric acid is to a large extent mediated via an activation of reflexes in the enteric nervous system

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Effects of substance P on inositol triphosphate accumulation, on contractile responses and on arachidonic acid release and prostaglandin biosynthesis in rabbit iris sphincter muscle

Cited by 32 publications

References 25 publications

Neurokinin‐1 receptor desensitization attenuates cutaneous active vasodilatation in humans

Neurokinin‐1 receptor desensitization attenuates cutaneous active vasodilatation in humans

Release of endothelium‐derived relaxing factor from pig cultured aortic endothelial cells, as assessed by changes in endothelial cell cyclic GMP content, is inhibited by a phorbol ester

Substance P effects on blood flow, fluid transport and vasoactive intestinal polypeptide release in the feline small intestine.

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