BASIM ZWAIN LECTURESMEDICAL PHYSIOLOGYCELL PHYSIOLOGY - 2

Professor Dr. Basim ZwainFaculty of Medicine

Jabir ibn Hayyan Medical Universitybasimzwain@jmu.edu.iq

CELL PHYSIOLOGY

Types of Cell Signaling1. Autocrine signaling – e.g. cytokine

interleukin-1 in monocytes2. Paracrine and juxtacrine signaling- e.g fibroblast growth factors 3. Endocrine signaling (various hormones)

CELL PHYSIOLOGY

CELL PHYSIOLOGYCell Signaling EventsA ligand or primary messenger binds a receptor associated with a target cell.Ligand binding results in conformational change and activation of the receptor.The activated receptor elicits a response in target cell, either directly or indirectly through production of second messenger.Target cell responses include alterations in cellular metabolism and in gene transcription.

CELL PHYSIOLOGY

Types of Receptor Classes

1. Intracellular receptors located in the cytoplasm or nucleus of the target cell

2. Cell surface receptors

CELL PHYSIOLOGYIntracellular receptors are bound by lipophilic ligands, which diffuse through plasma membrane. Ligand binding alters the receptor’s conformation, exposing the receptor’s DNA-binding domain.Receptors bind specific gene promoter elements and activate transcription of specific genes that results in the synthesis of specific proteins.An example is estrogen receptor in uterine smooth muscle cells.

CELL PHYSIOLOGYThere are four types of cell surface receptors:a. Nicotinic cholinergic receptors are linked to ligand-gated ion channels (eg, nicotinic AchRs).b. Catalytic receptors are transmembrane proteins that have intrinsic enzymatic (eg, serine or tyrosine kinase) activity.c. Other receptors are linked to proteins with enzymatic activity. (eg, cytokine receptor signaling through cytoplasmic tyrosine kinase).d. G-protein-linked receptors

G-protein-linked receptors have an extracellular ligand-binding domain and an intracellular domain that binds G-proteins. After ligand binding, receptors interact with G-proteins which are heterodimeric consist of α, β, and γ subunits that dissociate. G-proteins α-subunits bound to GTP interact with and activate specific membrane-bound enzymes, result in production of 2nd messengers that elicit responses in target cells. Adenylate cyclase & phospholipase systems are examples.

CELL PHYSIOLOGY

CLINICAL CONSIDERATIONS–Cholera toxin alters G-protein so that guanosine triphosphatase (GTPase) is unable to hydrolyze GTP, resulting in increased production of cAMP. Elevated cAMP in intestinal epithelial cells results in massive gut secretion of water and electrolytes, resulting in severe diarrhea and dehydration.–Pseudohypoparathyroidism results from a defective G-protein causes decreased cAMP levels with symptoms of hypoparathyroidism with normal or slightly elevated parathyroid hormone levels.

CELL PHYSIOLOGY

CLINICAL CONSIDERATIONS–Pertussis toxin blocks the activity of G1, allowing adenylate cyclase to stay active and increase cAMP.

CELL PHYSIOLOGY

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