Agonist Thus each type of R is specifie for the corresponding type of L. For example.

e which can combine with the receptor A ligand , thus may be a hormone or a drug molecule. R s are specific. That is, if a particular type of R is destined to combine with a specific ligand, say A, it will not combine with any other type of ligand (henceforth abbreviated, L). Agonist Thus each type of R is specifie for the corresponding type of L. For example. R for adrenalin will combine with adrenalin and following the combination, the post receptor events will occur and the effect. say glycogenolysis in hepatocyta occurs. Adrenalin is thus said to be the agonist for that receptor. Antagonists,, also called blockers art molecules which have a close (chemical) resemblance with the agonist molecule. Therefore, the antagonist molecule can and do occupy thereceptor site but there is some structural difference also so that post receptor events do not occur and because of the fact that the receptor sites are now occupied, the agonist molecules cannot occupy the R sites. For example, the action of adrenalin (the agonist) is blocked by propranolo.l Therefore, propranolol is a (B) blacker or adrenalin antagonist Srte (i) Receptors which bind thepepud* hormones an pr*sani on the ceH membrane, thai is, Ihey paniy pjouude mtha ECF and panly remain wrlhm the membrane, such R s are called, membrane bound receptors' (n) Receptors for thyroid and steroid hormones ait called 'cytosol receptors' because they occur either in the cytosol or on the nucleuls. Affinity A given type of R has affinity for its own ligand ...Thus R for adrenalin has affinity for adrenalin molecules. Binding This (ie.the binding between the R and L molecules) occurs by Van der Walls forte (intermodular attraction) and hydrogen bonds but not by covalent linkages. Recall, the binding by covalent linkages results in extremely strong binding (irreversible binding). Structure. An R has two domains (regions) (i) a ligand binding site, which binds with the ligand, it has affinity for its specific L and it can recognize the L (ii) then other domain is called the active site. This site is very important for tha post binding eventds, Further this she determines whether th e L is an agonist or antagonist and acts accordingly Movement After binding with the L. the R becomes PLC (receptoi-tigjnd camplex) and the RLc moves laterally within the cell membrane in case of membrane bound R Without this movement thepost briding events cannot occur. For this lateral movement, cytoskeletal structures are important (for cyloskeleton, see chap 1 sec.) Number, life, degradation it should be understood that since Langley first speculated about tht existence of a receptor in 1904 and till the late 1960s. the receptors were purely hypothetical substances, from many indirect evidences, people referred thai there are receptors but no direct proof was available. The picture has changed now and many informations about the Rs are pouring in rapidly. Yet only some discrete data are known and until the technology improves still further a comprehensive picture cannot be ejected with this background, thefallowings can be noted (i) R s are protemaceous macro molecules (n) in given cell, the receptor population of a grven species of R vanes; sometimes it increases, that isr goes up (up regulation) . sometimes it goes down (down regulation) (iii) Rs have a fixed life span (for example, the half life af insulin R is about 7 hr (iv) after theexpiry of life the R is degraded, Details; The receptor population tolls (down regulation) when too many ligand molecules are present. For example, the R of insulin, after binding with the L, goes into the cytosol, a phenomenon called internalization (NB. Before the binding. theR for insulin the in the membrane) After internalization, the R population will obviouily fall in the membrane. After internalization. some hgarrffs (eg insulin) are degraded along with the Rs. whereas with some other ligands after the intemalization the R is separated from the L and the R comes back (the phenomenon is called recycling) to the cell membrane. Using radio active markers, it is- now possible to make receptor counting POST BINDING EVENTS We now will discuss the events that follow the binding of R with its L So for as this chapter is concerned. L will mean only the agonists [not the antagonists) unless mentioned otherwise. what exactly will be the evente following the combination between the & and the L depend upon, whether (i) the R is m the membrane (membrane bound ). 0r (ii) in the cylosol or nucleus. EVENTS WHEN THE R IS MEMBRANE BOUND (Peptirde hormone). The events can be one of the several groups mentioned below Details. Gr A hormones. Binding with the membrane bound receptors lead to production of cyclic AMP (adenosin mono phosphate) abbreviated cAWP, which is a 2nd messenger. The hormone (ligand) which binds with the R is the first messenger (because it bungs messages regarding what is to be done by the target cell) and cAMP is the 2nd messenger. The message from the 1st messenger, thus, through a series of chemical events (see below) is handed over to a 2nd messenger. But this 2nd messenger (cAMP) is not normally present within the cell. It is formed from as precursor ATP withm the cell only when the Iist messenger has acted. Example Adrenalin the first messenger combines with R in the target cell in the membrane cAMP the 2nd messenger produced action of cAMP within the target cell leads to the final effect (eq glycogenolvsis). The 2nd messenger, cAMP. ultimately simulates an enzyme, protein kinase A the