352 POSTNATAL DEVELOPMENT OF α₁ ADRENERGIC RECEPTORS IN THE RAT HEART

Abstract

Myocardial contractility is mediated by both α and β adrenergic stimuli. α-Adrenergic agonist increases inotropic response independently of c-AMP and is thought to involve primarily α₁ adrenergic receptor (α₁AR) subtype present at postsynaptic receptor sites in the heart. Since sympathetic innervation of rodent myocardium develops postnatally it is also likely that developmental changes occur in the postsynaptic receptor sites. Thus we measured postnatal development of α₁ and β adrenergic receptors(βAR) in rat myocardium by binding experiments with ³H-prazosin and ³H-dihydroalprenolol (³H-DHA). ³H-Prazosin and ³H-DHA binding to rat ventricular membranes were rapid, saturable, stereospecific and reversible. The competition for ³H-Prazosin by agonists was in the order of Epinephrine= Norepinephrine≫Isoproterenol and that for ³H-DHA was Isop≫Epi=Norepi. The competition for ³H-Prazosin by antagonists was in the order of Prazosin>WB401>phentolamine≫Yohibimine and did not vary with age. The numbers of α₁AR and βAR sites in rat ventricular myocardium were:

There was no change in K_D (affinity) with age for either ligand. We conclude that the number of myocardial α₁AR increases rapidly after birth in rat myocardium and that the pattern is distinct from that of βAR. We speculate that the postnatal development of α₁AR and βAR is independently regulated in rat myocardium and that α₁AR are likely to be linked with postnatal neurosynaptic development while βAR are not.

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