Main classification of the receptor

Receptor

Receptor of the- Receptor of the- Ligand sensory nerve ending

Receptor of the ligand

Definition

• Receptor is the regulatory protein ,located on the surface or inside the target cell that serves to recognize the appropriate ligand and initiate the response to it, but itself has no other function.

Ligand

• It is signal triggering ion or molecule binding to a site on a target protein.

• Ligand binding to a receptor protein alter its chemical conformation.

• The conformational change determines the functional state of a receptor protein .

Some terms for the ligand-receptor interaction description.

1) Agonist: A ligand that can bind to a receptor and trigger a physiological response is called agonist for that receptor.

2) Partial agonist: ligand that binds to activate a given receptor, but has only partial efficacy at the receptor relative to a full agonist. They may also considered ligands which display both agonistic and antagonist effects when both a full agonist and partial agonist are present.

• The partial agonist actually act as a competitive antagonist competiting with the full agonist for receptor occupancy and producing the net decrease in the receptor activation observed with the full agonist alone.

• Ex- dichloroisoproterenol on beta adrenergic receptor, pentazocine on µ opiod receptor.

3) Inverse agonist: An agent that produces a response after activating the receptor in the opposite direction to that of the agonist. Ex-DMCM on benzodiazepin receptor.

4) Antagonist: An agent which prevents the action of an agonist on a receptor or subsequent response, but does not have any effect of its own.

Regulation• Up regulation:

suppose for a target cell , no

ligand is available. In this case , no receptor, specific for the chemical signal is occupied by the chemical signal. Therefore all the receptor in the cell are free to combine with the specific chemical signal and the receptors are in the state of maximum up regulation. If only a few of the receptors are occupied, then still, the receptors will be in a state of up regulation, though not maximum up regulation.

• Down regulation: When all the receptors are

occupied by the chemical signal molecules, the receptors are in a state of down regulation. When only some are occupied but others are free, the state is one of down regulation.

Specificity of receptor

• Post-ganglionic parasympathetic nerve secrete the ACh as NT. Cholinoreceptors can combine with ACh but not with NA.

• However, the some receptors can combine with ligand molecules which have minor differences between their chemical structure. Thus Ad and NA have only minor chemical difference between their structure,α-adreno receptor can combine with Ad and NA, that is both Ad and NA are agonist of α-adreno receptor.

• This phenomenon, however is not always true. Thus, there is no great difference between Ach and choline. However cholinoreceptor can readily bind with ACh but the affinity of choline for cholinoreceptor is negligible.

Classification

Ionotropic receptor

Metabotropic receptor

3 major pathway through which GPCRs function.

• Adenylyl cyclase- cAMP pathway• Phospholipase C- IP3-DAG pathway• Channel regulation.

cAMP pathway

• The PK-A phosphorylates and and alters the function of many enzymes, ion channels, transporters and structural protein to manifest as increased contractility in heart, relaxation in smooth muscle, glycogenolysis, lipolysis, inhibition of secretion/mediator release, hormone synthesis etc. In addition, cAMP directly opens a specific type of membrane Ca ion channels called CNG in the heart, brain and kidney. Responses opposite to the above are produced when AC is inhibited by inhibitory Gi protein, for ex- Ad and NA on α2 receptor.

IP3-DAG pathway

• The IP3 mobilises Ca ion from intracellular organellar depots and DAG enhances PKc activation by Ca ion. Cytosolic Ca ion act as a third messenger and is a highly versatile regulator acting through calmodulin, PKc and effectors-mediates/modulates contraction, secretion, eicosanoid synthesis, neuronal excitability, intracellular movements, membrane function, metabolism, cell proliferation etc.

Gene regulating receptors

Gene regulating receptors

Enzyme linked receptora)intrinsic enzyme receptor

• The intracellular domain either a protein kinase or guanylyl cyclase.

• In most case the protein kinase phosphorylates tyrosine residues on substrate proteins, e.g. insulin, EGF, NGF, but in few it is a serine or threonine protein kinase. In the monomeric state, the kinase remains inactive. Agonist binding induces dimerization of receptor molecules and activates the kinase to autophosphorylate tyrosine residues on each other, increasing their affinity for binding substrate proteins and carrying forward cascade of tyrosine phosphorylations.

• The enzyme can also be guanylyl cyclase as in the case of ANP. Agonist activation of the receptor generates cGMP in the cytosol as a second messenger which in turn activates cGMP- dependent protein kinase and modulates cellular activity.

2) JAK-STATE-kinase binding receptor

• Agonist binding induced dimerization alters the intracellular domain conformation to increase its affinity for a cytosolic tyrosine protein kinase JAK(JANUS-KINASE). On binding, JAK gets activated and phosphorylates tyrosine residue of the receptor, which now binds another free moving protein STAT(signal transducer and activator of transcription) which is also phosphorylated by JAK. Pairs of phosphorylated STAT dimerize and translocate to the nucleus to gene transcription resulting in biological response. Many cytokines, growth hormone ,interferon etc act through this type of receptor.

Functions

• To propagate regulatory signals from outside to within the effecter cell when the molecular species carrying the signal cannot itself penetrate the cell membrane.

• To amplify the signal.• To integrate various extracellular and

intracellular regulatory signals.• To adapt to short term and long term changes in

the regulatory melieu and maintain homeostasis.

Receptor of sensory nerve ending

Definition

• Receptors are the sensory nerve ending terminating in the periphery as the bare unmyelinated ending or specialized capsulated structure.

Classification

Receptor

Exteroceptor Interoceptor

Exteroceptor1)cutaneus

2) chemoreceptors

a) Taste budsb) olfactory cells

Taste buds

Olfactory receptor

Teloreceptor

• Rods and cones• Hair cells

Rods and cones

Hair cells

Interoceptor1) viscero-receptor

a) Stretch receptorb) Baro receptorc) Chemo receptord) Osmo receptor

Stretch receptor

Baroreceptor and regulation of visceral function

Chemoreceptor

Osmo receptor

2)Proprioceptor

Receptor • Muscle spindle.• Golgi tendon.• Pacinian corpuscle.• Free nerve ending.• Hair cells

Location • Muscle• Tendon• Ligament.• Fascia, joints.• Vestibular apparatus

Somatic Receptor: Muscle Spindle• are stretch receptors inthe muscle• – a type of

proprioceptorsense• organs that monitorthe position andmovements of body parts• more abundant inmuscles that require finecontrol

• Two types of intrafusalmuscle fibers basedanatomically on thelocation of their nuclei• Nuclear bag: thenucleiare located in the centerof the fiber, which bulgesout into a bag.• • Nuclear chain:thenucleispread out along the fiberlike a chain.• Only the ends of theintrafusal fibers containsarcomeres and are ableto contract

• Muscle Spindle• consist of modified muscle fibers(intrafusal fibers to distinguish them fromextrafusal fibers, i.e. the rest of themuscle)• only the two ends of an intrafusal fiberhave sarcomeres and are able to contract• middle portion acts as a stretch receptor

• Have three types of nerve fibers• Both contain primary afferent nerve fibers (Ia) which end inannulospiral fibers that coil around middle that respond

mainly tomuscle stretch• secondary afferent nerve fibers wrap primarily around the

ends ofnuclear chain fibers that respond mainly to prolonged strecth• gamma motor neurons fibers which innervate the ends of

theintrafusal fibers (constitutes about 1/3 of fibers in a spinal

nerve)

Adjustment of length of intrafusal fiber by gamma motor neuron.

Golgi tendon organ

• Golgi tendon organ stretch receptors are located within the tendons, detecting the amount of

stretch exerted by the muscles on the bones towhich they are attached; encode degree ofstretch by the rate of firing; don’t respond tolength, but to how hard it is pulling• synapse onto an interneuron in the spinal cordgray matter which then synapse onto therelevant alpha motor neuron, producinginhibitory (glycine) potentials• – decreases muscular contraction, prevents injury