Intercellular Communication

Department of Physiology School of Medicine University of Sumatera Utara

Intercellular Communication and Signal Transduction

The ability of cells to communicate with each other is essential for coordination of their diverse activities to maintain homeostasis as well as to control growth and development of the body as a whole

Intercellular Communication and Signal Transduction

Gap junctions Message transmission Directly from cell to cell Local Anatomic location Synaptic Across synaptic cleft Local Anatomic location & receptors Paracrine & Autocrine Endocrine

Local or general Specificity depends on

By By diffusion in circulating interstitial body fluids fluid Locally General diffused Receptors Receptors

Receptors for Hormones, Neurotransmitters, & Other Ligands

Proteins that are not static component of the cell, but their numbers increase & decrease in response to various stimuli, & their properties changes in physiologic conditions. Hormone/neurotransmitter active receptors (Down Regulation). Hormone/neurotransmitter active receptors (Up Regulation).

Mechanisms by Which Chemical Messengers Act

Mechanism
Open/close ion channels in cell membrane Act via cytoplasmic or nuclear receptors to increase transcription of selected nRNAs Activate phospholipase C with intracellular production of DAG, IP3, and other inositol phosphate Activate or imhibit adenylyl cyclase, causing increased or decreased intracellular production of cAMP

Examples
Ach on nicotinic cholinergis recepttor; norepinehrine on K+ channel in the heart Thyroid hormones, retinoic acid, steroid hormones Angiotensin II, norepinephrine via 1adrenergic receptor, vasopressin via V1 receptor. Norepinephrine via 1-adrenergic receptor (increased cAMP); norepinephrine via 2adrenergic receptor (decreased cAMP)

Increase cGMP in cell

Increase tyrosine kinase activity of cytoplasmic portions of transmembrane receptors Increase serine or threonine kinase activvity

ANP; NO (EDRF)
Insuline,EGF, PDGF,M-CSF TGF, MAPKs

G Proteins
Common way to translate signal to a biologic effect inside cells is by way of nucleotide regulatory proteins (G Proteins) that bind GTP. Signal reaches a G protein exchanges GDP for GTP effect. GTP
GTPase

GDP resting state.

GTPase activity is accelerated by RGS (Regulators of G protein signaling)

Diseases caused by loss-or gain of-function mutations of heterometric G-protein-coupled receptors and G proteins
Site Receptor Cone opsins Rhodopsin V2 vasopressin ACTH LH TSH Loss Loss Loss Loss Gain Gain Color blindness Congenital night blindness Two forms of retinitis pigmentosa X-linked nephrotic diabetes insipidus familial glucocorticoid deficiency Familial male precocious puberty Familial nonautoimmune hyperthyroidism Type of Mutation Disease

TSH
Ca2+ Thromboxane A2 Endothelin B

Loss
Gain Loss Loss

Familial hypothyroidism
Familial hypercalciuric hypocalcemia Congenital bleeding Hirschprungs disease
Last-1

Diseases caused by loss-or gain of-function mutations of heterometric G-protein-coupled receptors and G proteins
Site G protein Gs Gs Gs Gs Gi Loss Gain/Loss Gain (mosaic) Gain Gain Pseudohypothyroidism type 1a testotoxicosis McCune-Albright syndrome Somatotroph adenomas with acromegali Ovarian and adrenocortical tumors Type of Mutation Disease