Synonym |
Pituitary adenylate cyclase-activating polypeptide 38, PACAP-38 |
Species |
Human, Mouse, Ovine, Porcine, Rat |
Protein Accession |
P18509 |
Purity |
> 95% |
Endotoxin Level |
< 1.0 EU per 1 μg of protein |
Biological Activity |
Stimulates adenylate cyclase activity in CHO-K1 cells with EC50 of 0.18 nM |
Expression System |
E. coli |
Fusion Tag |
None |
Predicted Molecular Mass |
Approximately 4343 Da |
Formulation |
Lyophilized from a 0.2 µm filtered solution in PBS |
Reconstitution |
Centrifuge vial before opening. Reconstitute in sterile, deionized water to a concentration of
100 μg/ml. Do not vortex. This solution can be stored at 2-8°C for up to 1 week. |
Storage & Stability |
Store lyophilized protein at -20°C. Aliquot reconstituted protein and store at -20°C to -80°C.
Avoid repeated freeze-thaw cycles. |
FAQ
What is Acetyl-PACAP-38 and its primary function in biological research?
Acetyl-PACAP-38 is a
biologically significant peptide derived from the pituitary adenylate cyclase-activating polypeptide
(PACAP) family. Structurally, it is a peptide that exists in several naturally occurring forms, with
PACAP-38 being one of the most studied due to its longer amino acid chain. The acetylation of PACAP-38
enhances its stability, making it an attractive candidate for research purposes. This peptide has been
identified across various species, including humans, mice, ovines, and porcines, which signifies its
evolutionary importance and its conserved role in physiological processes. Acetyl-PACAP-38 is critically
involved in numerous biological functions. It is fundamentally known for its capability to activate
adenylate cyclase through its interaction with G protein-coupled receptors (GPCRs). The activation of
adenylate cyclase subsequently leads to an increase in cyclic AMP (cAMP) levels, which is a key
signaling molecule in cellular communication. This signaling cascade is essential in mediating a variety
of biological responses, such as neurotransmitter release, hormone secretion, and smooth muscle
relaxation. Additionally, it plays a vital role in neuroprotection, cognitive function, and circadian
rhythm regulation. Acetyl-PACAP-38 holds significant implications in neurological research. Its
neuroprotective properties have been linked to the ability to prevent apoptosis in neurons, which is of
particular interest for understanding and potentially treating neurodegenerative disorders such as
Alzheimer's and Parkinson’s diseases. Furthermore, studies have shown that Acetyl-PACAP-38 has a role in
the modulation of stress responses and influences neurogenesis and synaptic plasticity, which are
critical for learning and memory. Overall, the study of Acetyl-PACAP-38 in various species provides
remarkable insights into its diverse physiological and pathological roles. It facilitates a deeper
understanding of fundamental processes in neurobiology and endocrinology, drawing significant interest
from researchers aiming to translate these findings into therapeutic applications for a range of
conditions.
How is Acetyl-PACAP-38 used in research studies involving neurological and endocrine
systems?
In the context of research, Acetyl-PACAP-38 is a pivotal tool for studying the complex
interplay between the neurological and endocrine systems. Its varied roles include neurotransmission,
neuroprotection, and neurogenesis, making it an effective agent for exploring neuronal function and
development. Researchers utilize this peptide to investigate how signaling pathways are modulated and
what impact this has on cognitive processes and neuroplasticity. Acetyl-PACAP-38 is frequently used to
model neural processes and study diseases of the central nervous system. Given its neuroprotective
capabilities, studies often focus on understanding how it can prevent or mitigate neuronal damage. For
instance, in models of neurodegenerative diseases, Acetyl-PACAP-38 administration is investigated for
its ability to delay or attenuate the progression of pathology. This involves looking at how the peptide
reduces apoptosis in neuronal and glial cells and its potential role in enhancing the reparative
capacity of the nervous system. Experimentally, Acetyl-PACAP-38 is administered in various forms,
including in vitro cell cultures and in vivo animal models, to observe its effects on neuron viability,
differentiation, and network formation. Its interactions with specific PACAP receptors and downstream
signaling pathways are meticulously studied to elucidate mechanisms related to synaptic plasticity and
the modulation of neurogenic niches. The results of these experiments are critical in understanding the
neuroendocrine regulation of body processes including stress responses, circadian rhythm, and energy
homeostasis. In endocrine research, Acetyl-PACAP-38’s utility extends to studying the secretion dynamics
of various hormones. It is known to influence the release of hormones like insulin, growth hormone, and
cortisol, which marks its importance in the context of metabolic diseases, obesity, and stress-related
disorders. By examining the role of Acetyl-PACAP-38 in these mechanisms, researchers strive to unravel
the network of interactions that underlie normal physiology and pathophysiological conditions. The
peptide's role in coordinating cross-talk between the brain and peripheral organs provides insights into
hormonal regulation, making it a critical component in research exploring therapies for endocrine
disorders.
What are the key differences in the action of Acetyl-PACAP-38 across various
species?
Acetyl-PACAP-38 is a peptide conserved across a wide range of species, indicating its
evolutionary importance and fundamental role in biological systems. However, there are noteworthy
species-specific differences in its action that are crucial for researchers to consider when designing
and interpreting experiments. Each species' physiological context and the expression profiles of PACAP
receptors contribute to the nuanced effects observed. In humans and non-human primates, Acetyl-PACAP-38
is primarily noted for its significant roles in cognitive processes and neuroprotection. It helps in
regulating intricate brain functions such as memory, learning, and the response to stress. The effects
are modulated through various receptor subtypes in the central nervous system, and discrepancies in
receptor expression or affinity can lead to varying responses to the same peptide in therapeutic
studies. Hence, understanding its action in the human context offers insights into potential treatments
for neuropsychiatric disorders. In rodents such as mice, Acetyl-PACAP-38 similarly influences cognitive
functions but also provides a powerful model for studying stress-induced neurophysiological changes and
the interplay between neuroendocrine regulation and behavior. PACAP’s effect on mice has been leveraged
to unravel genetic and environmental interactions leading to anxiety and depression, where the peptide’s
modulatory actions on neurotransmitter systems are scrutinized. Meanwhile, in ovines (sheep) and
porcines (pigs), the focus often shifts toward metabolic and developmental influences. In these animals,
Acetyl-PACAP-38 has been shown to regulate feeding behaviors and energy homeostasis, which is crucial
for understanding obesity and metabolic syndromes in agricultural contexts. The peptide's influence on
reproductive functions and fetal development in livestock provides vital findings that can influence
breeding and health management practices. Despite the conservation of the peptide structure, distinct
physiological milieus and receptor interactions result in diverse biological outcomes between species.
Such differences necessitate comparative studies to translate findings effectively across species and to
apply such insights to human health and disease treatment strategies. Researchers need to account for
these interspecies variations in both experimental design and the interpretation of findings to harness
the full potential of Acetyl-PACAP-38 in translational science.
Can Acetyl-PACAP-38 have
therapeutic applications in human medicine, and what are the challenges?
Acetyl-PACAP-38 holds
significant promise for therapeutic applications in human medicine, largely due to its pleiotropic
effects on neuroprotection, neurogenesis, and hormonal regulation. However, the translation of its
beneficial properties into effective human therapies comes with a myriad of challenges that researchers
are diligently working to overcome. One of the most attractive features of Acetyl-PACAP-38 is its
neuroprotective potential, primarily in the context of neurodegenerative diseases such as Alzheimer's
and Parkinson's diseases. Its ability to mitigate cell death in neurons and support recovery from
neurological insult positions this peptide as a candidate for therapeutic development. By preventing
apoptosis and enhancing neuronal survival, Acetyl-PACAP-38 could theoretically slow disease progression
or even improve functional recovery in affected patients. Another prospective therapeutic avenue is its
application in mental health disorders, where it could modulate stress responses, anxiety, and
depression. However, developing Acetyl-PACAP-38-based treatments for these conditions is not without
significant hurdles. The complexity of the human brain and the diverse roles that PACAP receptors play
in different tissues complicate targeted therapy. Ensuring specificity in treatment to maximize benefits
while minimizing off-target effects is crucial. Researchers must also grapple with the intricacies of
the peptide's stability, bioavailability, and delivery. While acetylation enhances the stability of
PACAP-38, peptides in general tend to have short systemic half-lives and can be rapidly degraded by
proteolytic enzymes when administered. Innovative delivery systems, such as encapsulation in
nanoparticles or the use of delivery vectors, are being explored to enhance its pharmacokinetic profile.
These systems aim to ensure that adequate concentrations of the peptide reach target tissues in a
bioactive form. Developing therapeutic applications for Acetyl-PACAP-38 must also navigate the rigorous
safety and efficacy standards mandated by regulatory bodies. Comprehensive preclinical studies are
essential to establish pharmacological and toxicological profiles. These studies need to be followed by
carefully designed clinical trials to assess therapeutic potential and optimize dosing regimens.
Additionally, the cost of peptide synthesis and scale-up production processes are logistical challenges
that must be addressed to make such treatments economically viable. Overall, while Acetyl-PACAP-38
stands as a promising candidate for therapeutic application across various domains of human health, the
path from bench to bedside requires sustained research efforts and interdisciplinary collaboration to
address the existing challenges.
What are the potential side effects or risks associated with
using Acetyl-PACAP-38 in research or therapeutic settings?
When considering the use of
Acetyl-PACAP-38 in research or potential therapeutic applications, it is essential to acknowledge and
evaluate the prospect of side effects and risks that may accompany its administration. As with any
biologically active compound, the introduction of Acetyl-PACAP-38 into biological systems can lead to
unforeseen or unintended physiological responses that warrant careful investigation. In experimental
settings, most explorations of Acetyl-PACAP-38 focus on its positive biological outcomes due to its
action as a regulatory peptide affecting diverse signaling pathways. However, its broad range of
physiological roles means that balancing these effects is challenging, and disruptions can lead to side
effects. In particular, due to its role in neurotransmission and hormonal regulation, there is potential
for off-target effects that may arise from interactions with non-target PACAP receptors, or through
downstream effects that result from its primary action. Such interactions may result in undesired
alterations in mood, behavior, or circadian rhythms, especially given the central nervous system’s
sensitivity to neuropeptide modulation. Clinically, there is a potential risk for perturbations in
systems regulated by PACAP, such as cardiovascular and respiratory functions. The peptide's vasodilatory
properties, while potentially beneficial, could induce hypotensive events if not carefully monitored,
especially in susceptible individuals. Additionally, the modulation of hormonal pathways could
potentially lead to imbalances or dysregulation of endocrine functions. This is particularly noteworthy
in the context of metabolic diseases, where precise and controlled interventions are necessary to avoid
exacerbating existing conditions. In research contexts, the immunogenic potential of peptides like
Acetyl-PACAP-38 must also be considered. While acetylation adds to stability, it is crucial to assess
whether repeated or high-dose exposure might elicit immune reactions in model organisms, which could
confound experimental results or render the peptide ineffective over time. Moreover, for therapeutic
developments involving humans, the metabolic breakdown products of Acetyl-PACAP-38 need to be thoroughly
evaluated for any cytotoxic or adverse effects. Addressing these potential risks necessitates
comprehensive preclinical testing to determine safety profiles and establish dosing guidelines that
mitigate adverse outcomes. Ongoing monitoring and adaptation of experimental designs are critical in
anticipating and managing side effects effectively. Thus, while Acetyl-PACAP-38 presents substantial
potential for research and therapeutic applications, its safe implementation requires thorough
evaluation of its multifaceted interactions within biological systems accompanied by strategic oversight
to navigate the inherent risks.