Neuromodulatory effect of the atrial natriuretic factor clearance receptor binding peptide, cANF(4-23)-NH2 in rabbit isolated vasa deferentia.
This study tests the hypothesis that atrial natriuretic factor (ANF) and the ANF clearance receptor binding peptide, cANF(4-23)-NH2 (cANF), inhibit adrenergic and purinergic neurotransmission in the rabbit isolated vas deferens by a pertussis toxin (PTX)-sensitive mechanism. The vas deferens is a unique model used in the study of autonomic neurotransmission inasmuch as it has both a purinergic or twitch contraction and an adrenergic or tonic contraction associated with its response to electrical stimulation. Both ANF and cANF (10(-11) to 10(-6) M) inhibited electrically induced purinergic and adrenergic contractile force generation in a concentration-dependent manner. The ANF effect on both purinergic and adrenergic contractions was blocked by PTX (100 ng/ml). The cANF effect on the adrenergic contraction was also PTX-sensitive. Both peptides also attenuated evoked norepinephrine release in a concentration-dependent manner by a PTX-sensitive mechanism. cANF (10(-7) M) had no effect on norepinephrine- or ATP-induced contractions as was shown previously for ANF (10(-7) M). Therefore, the inhibitory effects of ANF and cANF appear to be prejunctional, on the release of the neurotransmitters, norepinephrine and ATP, from the nerve terminal and not postjunctional on the smooth muscle. An effect of cANF on neurotransmission suggests that the reputed "silent" ANF clearance receptor has biological activity. PTX-sensitivity suggests the involvement of a guanine nucleotide-binding protein in mediating the neuromodulatory effect of atrial peptides.
Johnson
B G
BG
Department of Pharmacology, University of Minnesota-Duluth, School of Medicine.
Trachte
G J
GJ
Drewett
J G
JG
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D004347:Drug Interactions; D004558:Electric Stimulation; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D037342:Pertussis Toxin; D011817:Rabbits; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000187:drug effects*; D014649:Vas Deferens / Q000187:drug effects* / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D010566:Virulence Factors, Bordetella; C065367:atrial natriuretic factor (4-23)NH2, de-Gln(18)-de-Ser(19)-de-Gly(20,22)-de-Leu(21)-; D009320:Atrial Natriuretic Factor; D037342:Pertussis Toxin; D017461:Receptors, Atrial Natriuretic Factor; D009638:Norepinephrine