Integrated Human Physiology

Integrated Human Physiology

1. Cell signalling- paracrine (nearby), autocrine (self), endocrine (in blood), juxtacrine (direct contact)

   • Initiated through process of signal transduction (transmission of molecular signals from exterior to interior)
     • As a results of activation of receptors
       • Ionotropic receptors- ligand gated transmembrane ion channels
         • More specifically classified as...
           • Mechanoreceptors
             • Examples- Baroreceptors
           • Steroid receptors- intracellular based responding to steroid molecules such as...
             • Testosterone & oestrogen
               • Steroid molecules regulate transcription- complex (dimer) specific to DNA sequence binds to promoter region upstream of gene of interest
           • Enzyme-linked receptors
             • Examples- Tyrosine kinase receptor & VEGF receptor- both respond to growth factors E.g. VEGF, IGF-I
               • Growth factors stimulate growth, proliferation, healing, differentiation, apoptosis
               • Tyrosine kinase activation-->activation of kinase leads to autophosphorylation of tyrosine residues in cytosol
           • Ion channels
             • Example- nicotinic receptor
               • Located at pre-ganglionic nerve terminals of...
               • Respond to acetylcholine- fast synaptic transmission
           • GPCRs
             • Example- muscarinic receptor
               • Located at post-ganglionic nerve terminals of...
                 • Parasympathetic NS
               • Located at sweat glands
                 • Sympathetic NS
               • involves secondary messengers- slow response
             • Example- alpha/beta adrenergic receptors
               • Located at post-ganglionic nerve terminal of...
               • Alpha receptors stimulated by adrenaline & noradrenaline
               • Beta 1 receptors stimulated by adrenaline & noradrenaline, Beta 2 receptors stimulated by adrenaline
             • GTP (active form), GDP (inactive form), GTPase hydrolyses GTP into GDP
             • Subunits= alpha, beta & gamma- when activated dissociates into G-alpha + beta-gamma complex (GI complex inhibits cAMP production, GS complex stimulates cAMP production
       • Metabotropic receptors- ligand gated transmembrane proteins
       • Activation leads to initiation of secondary messenger systems
         • Leading to signal amplification- triggers chain of events and intensifies signal
           • Via enzymes/kinases
             • End point it to modulate cell function
             • Involved in phosphorylation (ATP donates phosphate)- serine, threonine, tyrosine, histidine residues
         • Example- adenalyte cyclase & phospholipase
           • Adenalyte cyclase synthesises cAMP from ATP which activates PKA
           • Phospholipase hydrolyses phospholipids into DAG (stays in membrane) + iP3 (cleaved off)
             • iP3 diffuses to endoplasmic reticulum & binds to & opens ligand gated ion channels (Ca2+ moves out into cytosol)
             • DAG activates PKC ( phosphorylates proteins= activation)