Expression of opioid receptors during heart ontogeny in normotensive and hypertensive rats.
BACKGROUND
The opioidergic systems are involved in modulating nociceptive stimuli. In addition, the recent results suggest that endogenous and exogenous opioids could play a role in the modulation of blood pressure and cardiac functions. However, little is known regarding the expression and role of opioid-binding sites in the heart. The decreased sensitivity to noxious stimuli in hypertensive rats raises the possibility of different developmental pattern expression of opioid-binding sites in normotensive versus hypertensive rats.


RESULTS
Opioid receptor expression in hearts from hypertensive and normotensive rats was studied during heart development by binding assays. From P1 until P90, the development of the heart in the two rat strains was accompanied by a gradual increase in the density of kappa-opioid receptors. Hearts from hypertensive rats expressed significantly higher levels of kappa receptors compared with those of normotensive rats. At ages older than P7, mu-opioid receptors could not be detected in hearts of both strains, whereas delta-opioid-binding sites gradually increased until reaching adult levels. Seven-day-old cardiomyocyte cultures of both rat strains expressed similar densities of delta or kappa receptors to those observed in hearts from 7-day-old neonates. The mu-binding sites were not detected in cardiomyocytes cultures. Similar to the in vivo state, cultured myocytes from hypertensive rats had significantly higher levels of kappa-binding sites (1.5 fold) compared with those of normotensive rats. The kappa sites are pertussis toxin sensitive, and the state of coupling of the receptor to G protein is similar for the two rat strains.


CONCLUSIONS
The role of opioid-binding sites in the heart is not completely clear. Hypertensive rats are known to be less sensitive to noxious stimuli compared with normotensive rats. It is controversial whether the site if application of noxious stimuli plays an important role in the sensitivity to pain in hypertensive rats. We suggest that the opioidergic system could play a role in the modulation of blood pressure in addition to its known effect on nociception.
Zimlichman
R
R
Department of Internal Medicine, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Gefel
D
D
Eliahou
H
H
Matas
Z
Z
Rosen
B
B
Gass
S
S
Ela
C
C
Eilam
Y
Y
Vogel
Z
Z
Barg
J
J
D000818:Animals; D000831:Animals, Newborn; D001665:Binding Sites; D002478:Cells, Cultured; D006973:Hypertension / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011957:Receptors, Opioid / Q000032:analysis*; D017465:Receptors, Opioid, delta / Q000032:analysis; D017473:Receptors, Opioid, kappa / Q000032:analysis*
D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa