Substance P (SP) & Endorphin

Content

• Neuropeptides & pain perception– Substance P– endorphins

• NK1-receptor & Central opiate receptors• Endorphins• Enkephanlin

Substance P (SP)•a kind of neuropeptide (belongs to the tachykinin neuropeptide family)•Mainly found in the brain and spinal cord•Substance P is an important element in pain perception

tachykinin family• tachykinin family ： Phe-X-Gly-Leu-Met-

NH2 X is either an Aromatic( 苯環類 )

or an Aliphatic amino acid( 酯胺酸 )

Substance P

NK1-receptor

• The endogenous receptor for Substance P is neurokinin 1 receptor (NK1-receptor, NK1R).

• NK1-receptor belongs to the tachykinin receptor sub-family of GPCRs(G-protein couple receptor)

• NK1-receptor is considered an attractive drug target, particularly with regards to potential analgesics and anti-depressants

Tachykinin peptides Substance p

Mammalian tachykinin receptor NK-1 (most attractive)

NK-2

NK-3

……

….

Function of Substance P

• SP has been associated with the regulation ofmood disorders, anxiety, stress , etc.

• SP also relates to Neurogenic inflammation• Substance P receptor(NK1-receptor)

antagonists may have important therapeutic applications in the treatment of a variety of stress-related illnesses, in addition to their potential as analgesics

Other application• Cell growth ： Substance P has been known to

stimulate cell growth in culture, and it was shown that Substance P could promote wound healing of non-healing ulcers in humans

• Diabetes ： Substance P has also been shown to reverse diabetes in mice but effects to insulin secretion seems to be species dependent.

• Vasodilation ： It has been shown that vasodilatation to substance P is dependent on the NK1 receptor located on the endothelium.

• Why may a runner who twists his leg during a competition finish the run before he really feels the pain?

Central opiate receptors

• The endogenous analgesia system is a pain control system descending from brainstem to the spinal cord.

• Endogenous opioids are substances with opiate-like effects.

• occurring in the nervous system – ß -endorphin,met-enkephalin, leu-enkephalin,

dynorphin and many others

• Endogenous opioids are derivatives of three large protein molecules encoded by three different genes. – e.g.

ACTHPOMC ß -endorphin

Nerve impulse Spinal cord Endorphins

( － ):releasing pain signals

Stimulation or increased tone of the analgesia system can suppress strong pain signals entering the spinal cord through the dorsal spinal horn.

背部

腹部

Endorphin

• endogenous opioid neuropeptides • function as neurotransmitters• produced by the pituitary gland and the

hypothalamus • during exercise,excitement, pain, consumption

of spicy food, love and orgasm,• resemble the opiates in their abilities to

produce analgesia and a feeling of well-being

“endo-”

morphineendogenous

“–orphin”

Enkephalin

• An enkephalin is a pentapeptide involved in regulating nociception in the body.

Met-enkephalin

• The enkephalins are termed endogenous ligands, or specifically endorphins

• they are internally derived and bind to the body's opioid receptors.

– Met-enkephalin is Tyr-Gly-Gly-Phe-Met.– Leu-enkephalin has Tyr-Gly-Gly-Phe-Leu.

資料來源：• http://en.wikipedia.org/wiki/Beta-endorphin• http://en.wikipedia.org/wiki/Substance_P• http://en.wikipedia.org/wiki/Brainstem• http://tw.knowledge.yahoo.com/question/question?

qid=1405111805839• http://tw.knowledge.yahoo.com/question/question?

qid=1005010501521• Campbell biology campbell reece 8th edition by Reece,

Campbell 2007 •