bs148h 23 October 2007Read: Text ch 45 • endocrine system• Para-Neuro-Endo Sys• Prostaglandins-COX-Pain • Feedback & Fever• Receptors & 'Meaning‘• Ancient Origins • Classic Hormones• Steroid Hormones• Endocrine Disrupters• Peptide-Protein Hormones• Caffeine - G-coupled• Hypothalamus-Pituitary• PheromonesThe The NeuroNeuroEndocrineEndocrineSystemSystemis an integrated network: is an integrated network: regulates homeostasishomeostasis in the face of perturbations (ex: body temp, posture), initiates adaptive changeadaptive change in response to signals/cues (ex: fever, movement)PheromonesPheromones are chemical signals to the neuroendocrine sys of other individuals!They’re all part of a continuum:Hormones from anterior pituitaryanterior pituitary (ACTH, GH, TSH, LH, FSH, PRL, MSH)under local control by ‘releasing factors’ from hypothalamus (Fig 45.8);‘Hormones’ from posterior pituitaryposterior pituitary (ADH & oxytocin) secreted by neurons w/ cell bodies in hypothalamus (Fig 45.7);‘Hormones’ from adrenal medullaadrenal medulla (epinephrine & norepinephrine)are neurotransmitters from modified neural crest cells; HormonesHormones secreted into bloodby endocrine glandsendocrine glandsact on receptor proteinsreceptor proteinswhich determine consequencesinside target cells; target cells; Table 45.1:“classic hormones”NeurohormonesNeurohormones are secreted into the blood from neurons; ex: ADH from hypothalamic osmoreceptor neurons via posterior pituitary →↑ kidney reabsorption of H2OParacrineParacrine signals are local signals to nearby cells; ex: NO & vasodilation; cytokines & leukocyte recruiting, etc Fig 11.4Molecular mechanisms of nociceptionnociception. Julius D & A Basbaus 2001 Nature 413:203-210.… are one of the chemical signals (cytokines) that recruit phagocytes to wounds and potentiatepotentiatepainpain - to get your attention.http://www.uic.edu/labs/mesecar/lecture_2.htmCOX-1 maintains prostaglandin synthesis in the stomach, kidneys, and platelets. Prostaglandins: Prostaglandins: widespread & diverse group of paracrineparacrinesignalssignals1stfound in seminal fluid, from prostate: stimulate contraction of uterine smooth muscle {of another person!}Non-selective NSAIDsinhibit COX-1& COX-2COX-2 inhibitors selectively inhibit COX-2COX-2 maintains prostaglandin production predominately in inflamed tissuePGE2Celebrex ↑ heart attacksOpiatesOpiates & cannabinoidscan counteract the increase in excitability of the nociceptor.When nociceptors {pain nerves} are exposed to injury and inflammation, their excitability is altered.The figure highlights the vanilloid receptor VR1 {stimulated by heat & chemicals like capsaicinto ↑ Na+ influx }ProstaglandinsProstaglandins PGE2enhance nociceptor excitability:↑ Na+influx @ TTX-RVR1PGE2 {note: G-coupled}Editor's Summary9 November 2006A taste for painThree peptides isolated from the venom of the West Indian tarantThree peptides isolated from the venom of the West Indian tarantula ula ......have been found to promote pain and inflammation have been found to promote pain and inflammation by activating the same neuronal receptor as capsaicin, by activating the same neuronal receptor as capsaicin, the hot component of the hot component of chillichillipepperspeppers. ...News and Views:Physiology:Physiology:ChannelledChannelledpainpainLesley Anson Full TextThe newly isolated peptides are dubbed 'vanillotoxins' because of their action on the TRPV1 vanilloid receptor ...{formerly known as VR1}Letter:Spider toxins activate the capsaicin receptor Spider toxins activate the capsaicin receptor to produce inflammatory painto produce inflammatory painJ. Siemens et al. Full TextWhy a Diet Rich in Seafood is HealthyWhy a Diet Rich in Seafood is HealthySci. STKE, 17 October 2006Vol. 2006, Issue 357 OmegaOmega--3 fatty acids3 fatty acids, {“essential” polyunsaturated fatty acids}{omega-3s must be obtained from food ... such as cold-water fish including tuna, salmon, and mackerel... in dark green leafy vegetables, flaxseed oils, and certain vegetable oils.} have been associated with beneficial health effects. One mechanism for their antitheir anti--inflammatory effect is via inflammatory effect is via competitive inhibition of the enzymatic activity of competitive inhibition of the enzymatic activity of cyclooxygenasecyclooxygenase(COX), (COX), which is the ratewhich is the rate--limiting step in the biosynthesis of prostaglandins.limiting step in the biosynthesis of prostaglandins.Massaro et al. (2006 Proc. Natl. Acad. Sci. U.S.A. 103, 15184) report that exposure of vascular endothelial cells exposure of vascular endothelial cells to the omega-3 fatty acid docosahexaenoate (DHA) for periods long enough for it to be incorporated into cellular membranes inhibits the ... expression of inhibits the ... expression of COXCOX--22and prostaglandin production and prostaglandin production in response to the in response to the proinflammatoryproinflammatorysignal interleukinsignal interleukin--1 (IL1 (IL--1 ).1 ). ...Bacon That's Good For You? Researchers Create Pigs Bacon That's Good For You? Researchers Create Pigs That Produce HeartThat Produce Heart--healthy Omegahealthy Omega--3 Fatty Acids3 Fatty AcidsScienceDaily (Mar. 27, 2006)... representing the first cloned transgenic livestock that can make the beneficial compound. PhytochemistryPhytochemistry::IbuprofenIbuprofen--like activity in extralike activity in extra--virgin olive oilvirgin olive oilBeauchamp et al. Nature 437, 45-46 (1 September 2005) Newly pressed extraextra--virgin olive oil containsvirgin olive oil containsoleocanthaloleocanthal —a compound whose pungency induces a strong stinging sensation in the throat, not unlike that caused by the non-steroidal anti-inflammatory drug ibuprofen. The bitterness of certain compounds is correlated with their pharmacological activity ... we therefore tested whether oleocanthal might mimic the pharmacological effects of ibuprofen, a non-selective inhibitor of cyclooxygenase enzymes COX-1 & COX-2.We show here that ... oleocanthaloleocanthalacts as a natural antiacts as a natural anti--inflammatory compoundinflammatory compoundthat has a potency and profile strikingly similar to that of ibuthat has a potency and profile strikingly similar to that of ibuprofen.profen.... both these molecules inhibit the same ... both these molecules inhibit the same cyclooxygenasecyclooxygenaseenzymes enzymes in the