[Arg8]vasotocin excites neurones in the dorsal vagal complex in vitro: evidence for an action through novel class(es) of CNS receptors.
Using extracellular recordings from brainstem slices in vitro, it was demonstrated that a high proportion (38/56) of neurones in the dorsal vagal complex of dioestrus, virgin female rats exhibit an excitatory response to [Arg8]-vasotocin (AVT). Pharmacological characterization suggests that these responses cannot be entirely explained by interaction with either of the currently known classes of central receptors for oxytocin (OT) and vasopressin (V1a). Comparison of the responses with those to the OT receptor-specific agonist [Thr4,Gly7]-OT (TGOT), showed that not all neurones that responded to TGOT also responded to AVT (3/27). Furthermore, while the effects of 10(-7) M TGOT could be blocked either by the broad-spectrum antagonist d(CH2)5[d-Tyr(OEt)2,Val4,Cit8]-vasopressin or by the selective OT receptor antagonist d(CH2)5[Tyr(Me)2,Thr4,Orn8,Tyr-NH2(9)]-vasotocin, these peptides did not completely block the responses to AVT, indicating that AVT is unlikely to act through the central OT receptor. The responses to AVT and [Arg8]-vasopressin (AVP) indicated the presence of at least 2 classes of receptor with which these agonists could act. Of 42 neurones tested with both AVP and AVT, none responded to AVP in the absence of a response to AVT, while 7/42 responded to AVT without a response to AVP. This might be explained by AVP acting through only the V1 receptor, while AVT acts through both the V1 and its own novel class of receptor. This was substantiated by the fact that two OT/V1 receptor antagonists, d(CH2)5[d-Tyr(OEt)2,Val4,Cit8]-VP and d(CH2)5[Tyr(Me)2,Tyr-NH2(9)]-AVP, were unable to block completely all the responses to AVT at a dose which suppressed responses to both AVP and TGOT.(ABSTRACT TRUNCATED AT 250 WORDS)
Ingram
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CD
Department of Anatomy, School of Medical Sciences, University of Bristol, UK.
Tolchard
S
S
D000595:Amino Acid Sequence; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000494:pharmacology; D004031:Diestrus; D004594:Electrophysiology; D005260:Female; D008526:Medulla Oblongata / Q000187:drug effects* / Q000502:physiology; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010121:Oxytocin / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018045:Receptors, Oxytocin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D017483:Receptors, Vasopressin / Q000819:agonists / Q000502:physiology*; D014667:Vasopressins / Q000494:pharmacology; D014668:Vasotocin / Q000031:analogs & derivatives / Q000494:pharmacology*
D065092:Antidiuretic Hormone Receptor Antagonists; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; C034862:vasotocin receptor; D014667:Vasopressins; D001127:Arginine Vasopressin; C076093:vasotocin, (beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)-O-methyl-Tyr(2)-Thr(4)-Orn(8)-Tyr(9)-NH2; C033683:oxytocin, tri-Gly-; D010121:Oxytocin; C067260:vasopressin, beta-mercapto beta,beta-cyclopentamethylenepropionic acid(1)-O-ethyl-Tyr(2)-Val(4)-Cit(8)-; D014668:Vasotocin