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 Synaptic Paracrine & Endocrine
junctions Autocrine
Message Directly Across By By
transmission from cell synaptic diffusion in circulating
to cell cleft interstitial body fluids
fluid
Local or Local Local Locally General
general diffused
Specificity Anatomic Anatomic Receptors Receptors
depends on location location &
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
Increase cGMP in cell
Increase tyrosine kinase activity of cytoplasmic
portions of transmembrane receptors
Increase serine or threonine kinase activvity
Examples
Ach on nicotinic cholinergis recepttor;
norepinehrine on K+ channel in the heart
Thyroid hormones, retinoic acid, steroid
hormones
Angiotensin II, norepinephrine via 1-
adrenergic receptor, vasopressin via V1
receptor.
Norepinephrine via 1-adrenergic receptor
(increased cAMP); norepinephrine via 2-
adrenergic receptor (decreased cAMP)
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.
GTPase
GTP 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 Type of Mutation Disease

Receptor
Cone opsins Loss Color blindness
Rhodopsin Loss Congenital night blindness
Two forms of retinitis pigmentosa
V2 vasopressin Loss X-linked nephrotic diabetes insipidus
ACTH Loss familial glucocorticoid deficiency
LH Gain Familial male precocious puberty
TSH Gain Familial nonautoimmune hyperthyroidism
TSH Loss Familial hypothyroidism
Ca2+ Gain Familial hypercalciuric hypocalcemia
Thromboxane A2 Loss Congenital bleeding
Endothelin B Loss Hirschprung’s disease
Last-1
 Diseases caused by loss-or gain –of-function mutations of
heterometric G-protein-coupled receptors and G proteins

Site Type of Mutation Disease

G protein
Gs  Loss Pseudohypothyroidism type 1a
Gs  Gain/Loss testotoxicosis
Gs  Gain (mosaic) McCune-Albright syndrome
Gs  Gain Somatotroph adenomas with acromegali
Gi  Gain Ovarian and adrenocortical tumors