PMID- 1280738
OWN - NLM
STAT- MEDLINE
DCOM- 19921231
LR  - 20161123
IS  - 0160-2446 (Print)
IS  - 0160-2446 (Linking)
VI  - 20
IP  - 5
DP  - 1992
TI  - Cardiovascular effects of omega-conopeptides in conscious rats: mechanisms of 
      action.
PG  - 756-64
AB  - We examined the effects of omega-conopeptides, a novel class of neuronal 
      voltage-gated calcium channel antagonists, on hemodynamic responses in rats. 
      Intravenous (i.v.) injections of SNX-111 (omega-conopeptide MVIIA) 
      dose-dependently decreased arterial blood pressure (BP) in conscious rats. 
      Intracerebroventricular (i.c.v.) SNX-111 injections (580 pmol) tended to increase 
      BP and, after an initial decrease, to increase heart rate (HR). The dose-response 
      curve for SNX-111 administered i.v. in conscious rats was biphasic. Beginning at 
      subdepressor doses, SNX-111 caused a long-lasting blockade of pressor responses 
      elicited by sympathetic nerve stimulation in pithed animals but did not prevent 
      increases in BP evoked by exogenously administered norepinephrine (NE). 
      Pretreatment of rats with histamine antagonists partially blocked the hypotensive 
      effects of the higher (870 and 2,900 nmol/kg) doses of SNX-111. Substitution of 
      alanine for arginine at position 10 ([Ala10]-MVIIA) markedly attenuated the 
      histamine-mediated component of the vasodepressor response. Together, these 
      findings indicate that SNX-111 administered i.v. decreases systemic BP by a 
      combination of blockade of sympathetic neurotransmission and mast cell 
      degranulation; the latter function appears to be dependent on the arginine 
      residue in position 10 of the amino acid sequence of SNX-111.
FAU - Bowersox, S S
AU  - Bowersox SS
AD  - Neurex Corporation, Menlo Park, California 94025.
FAU - Singh, T
AU  - Singh T
FAU - Nadasdi, L
AU  - Nadasdi L
FAU - Zukowska-Grojec, Z
AU  - Zukowska-Grojec Z
FAU - Valentino, K
AU  - Valentino K
FAU - Hoffman, B B
AU  - Hoffman BB
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Cardiovasc Pharmacol
JT  - Journal of cardiovascular pharmacology
JID - 7902492
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Peptides)
RN  - 0 (Peptides, Cyclic)
RN  - 0 (omega-Conotoxins)
RN  - 107407-86-3 (Conus magus toxin)
RN  - 3U6IO1965U (Chlorpheniramine)
RN  - 7I64C51O16 (ziconotide)
RN  - 80061L1WGD (Cimetidine)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Blood Pressure/*drug effects
MH  - Calcium Channel Blockers/*pharmacology
MH  - Chlorpheniramine/pharmacology
MH  - Cimetidine/pharmacology
MH  - Decerebrate State
MH  - Dose-Response Relationship, Drug
MH  - Heart Rate/*drug effects
MH  - Injections, Intraventricular
MH  - Male
MH  - Molecular Sequence Data
MH  - Norepinephrine/pharmacology
MH  - Peptides/administration & dosage/*pharmacology
MH  - Peptides, Cyclic/administration & dosage/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *omega-Conotoxins
EDAT- 1992/01/01 00:00
MHDA- 1992/01/01 00:01
CRDT- 1992/01/01 00:00
PHST- 1992/01/01 00:00 [pubmed]
PHST- 1992/01/01 00:01 [medline]
PHST- 1992/01/01 00:00 [entrez]
PST - ppublish
SO  - J Cardiovasc Pharmacol. 1992;20(5):756-64.